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Steroid Withdrawal Syndrome

Corticosteroid Withdrawal Syndrome

Steroid withdrawal syndrome, the leading cause of adrenocortical insufficiency, results from the abrupt cessation of steroid therapy. The clinical picture includes non-specific features such as malaise, lethargy, low-grade fever, headache, myalgia, arthralgia, mood changes, etc. The diagnosis is confirmed with biochemical testing.


Presentation

Steroid withdrawal syndrome, the most frequent causative factor of acute adrenocortical insufficiency, occurs in the context of a normal hypothalamic-pituitary-adrenal axis (HPA) [1]. Its manifestations are related to glucocorticoid deficiency, which is a consequence of endogenous suppression of cortisol as a result of steroid therapy [2]. Glucocorticoids are prescribed for its anti-inflammatory and immunosuppressive effects [3] for the management of autoimmune and inflammatory conditions, allergic reactions, and neoplastic diseases [4]. Symptoms can develop in patients who have discontinued steroid therapy whether the drug was taken in multiple doses or just once, and even in healthy people without disease [1]. Overall, this syndrome is self-limiting and can be treated with small doses of glucocorticoids [5]. A very important consideration for individuals who have completed treatment is that exogenous glucocorticoids should be gradually and slowly tapered off to prevent adrenal insufficiency and its sequelae.

The presentation of steroid withdrawal syndrome shares similar characteristics to that of adrenal insufficiency [2]. Specifically, the clinical picture may include malaise, weakness, lethargy, hyposthenia, nausea, emesis, anorexia, weight loss, diffuse headaches, postural hypotension, myalgia, arthralgia, mood changes, and emotional lability [5] [6] [7]. Patients may also develop a temporary low-grade fever [6]. Additionally, skin desquamation may be observed in affected individuals [6] [7].

Studies have reported steroid withdrawal syndrome in pulmonary tuberculosis patients who tapered off prednisone and adrenocorticotropic hormone (ACTH) after using these therapies for 3 months and tapering off steroids over a period of 3 weeks [6]. Another investigation noted that patients taking cortisone for chronic asthma also developed symptoms after cessation [8]. Additionally, children on dexamethasone experienced such effects following discontinuation of the steroid [7].

Fatigue
  • We ask about general symptoms (anxious mood, depressed mood, fatigue, pain, and stress) regardless of condition. Last updated: November 24, 2018[patientslikeme.com]
  • The most significant symptoms of SWS documented were fatigue in 70 patients (60.3%) and anorexia in 32 (27.6%). Four elderly patients (3.4%) suffered with serious SWS symptoms of grade 3.[jlc.jst.go.jp]
  • Weight Loss: There is a rapid weight loss which may lead to extreme fatigue. Sudden Dip in Blood Pressure: A person might experience a drop in blood pressure levels, even if the person is not a patient of low blood pressure.[buzzle.com]
  • “Steroid withdrawal symptoms can include dizziness, fatigue, intestinal upset, and headaches. These may occur as the body adjusts to the reduction in steroid supplementation and starts making its own steroids.[sobadass.me]
Goiter
  • MORPHOLOGY OF THE PITUITARY 19 THE OPTIC CHIASM IN ENDOCRINOLOGIC 204 PARANEOPLASTIC ENDOCRINE 223 SEX HORMONES AND HUMAN 219 APPROACH TO THE PATIENT WITH 37 ADVERSE EFFECTS OF IODIDE 360 MORPHOLOGY OF THE THYROID 38 NONTOXIC GOITER 366 SYNTHESIS AND[books.google.de]
  • It is also used to treat symptoms of benign prostatic hyperplasia (BPH) in men with an enlarged prostate. 0.83 Generic Synthroid Generic Synthroid is used for treating low thyroid activity and treating or suppressing different types of goiters.[shiprxforumuncp.gq]
  • Hyperthyroidism Hyperthyroidism is a common disease affecting around 2 percent of women and 0.2 percent of men. 20 Graves' disease is the most common cause of thyrotoxicosis, but other causes are toxic nodular goiter and toxic adenoma. 21 Graves' disease[aafp.org]
Thyroid Nodule
  • MORPHOLOGY OF THE PITUITARY 19 THE OPTIC CHIASM IN ENDOCRINOLOGIC 204 PARANEOPLASTIC ENDOCRINE 223 SEX HORMONES AND HUMAN 219 APPROACH TO THE PATIENT WITH 37 ADVERSE EFFECTS OF IODIDE 360 MORPHOLOGY OF THE THYROID 38 NONTOXIC GOITER 366 SYNTHESIS AND 39 THE THYROID[books.google.de]
Loss of Appetite
  • It has now been almost a year and I suffer symptoms such as generalized pain/aches/soreness, loss of appetite, lack of energy, etc.[csrf.net]
  • When used in combination with chemotherapy, steroids may enhance the killing of lymphoma cells, and also help mitigate (reduce) fatigue, nausea, and loss of appetite associated with chemotherapy.[lymphomation.org]
  • Symptoms from withdrawal from anabolic steroids include : Mood swings Serious depression Fatigue and excessive sleeping Restlessness Loss of appetite Trouble sleeping or insomnia Decreased sex drive Cravings for steroids If a person presents with manic[americanaddictioncenters.org]
  • The most common symptoms are severe fatigue, loss of appetite, weight loss, nausea, vomiting, diarrhea, muscle weakness, irritability, and depression.[nadf.us]
  • He has had loss of appetite, but never was a big eater anyway. Looks like these symtoms can last weeks to months depending on how long one has been on the drug. Medical monitoring is highly recommended. Don't do this on your own.[topix.com]
Failure to Thrive
Hypotension
  • Specifically, the clinical picture may include malaise, weakness, lethargy, hyposthenia, nausea, emesis, anorexia, weight loss, diffuse headaches, postural hypotension, myalgia, arthralgia, mood changes, and emotional lability.[symptoma.com]
  • […] tapering off prednisone can lead to insufficient cortisol levels in the blood and, subsequently, prednisone withdrawal symptoms that include the following: General body weakness or fatigue Muscle weakness Body aches Headaches Fever Low blood pressure (hypotension[drugsdb.com]
  • These symptoms include (but are not limited to) arthralgias, malaise, fever, anorexia, nausea, weakness, weight loss, lethargy, hypotension, abdominal pain, hyponatremia, hyperkalemia, and vomiting.[clinicaladvisor.com]
  • In the absence of corticosteroids, stress results in hypotension, shock, and death.[emedicine.medscape.com]
  • The following symptoms and signs may occur in individuals that are withdrawing from taking steroids: Weakness Fatigue Decreased appetite Weight loss Nausea Vomiting Diarrhea Abdominal pain Low blood pressure ( hypotension ) Dizziness or fainting Low blood[rxlist.com]
Orthostatic Hypotension
  • hypotension, nausea, vomiting, anorexia, weight loss, fever, hypoglycemia, desquamation of skin.[aafp.org]
Papule
  • In addition, a significant number of the patients had papules/ nodules (61%), pustules (47%), swelling (43%), dryness and cracked skin (41%), dilation of the blood vessels (35%), subsequent peeling of the skin (33%).[drwangskincare.com]
  • Swelling ( oedema ) and papules can occur. The usual symptom described by patients is burning and/or stinging. Itch may also be reported, especially once the redness starts to fade and the dry scaly (desquamative) phase begins.[dermnetnz.org]
  • It can be differentiated from the erythematoedematous type by the presence of papules (pimple-like bumps), nodules (deeper bumps), pustules, redness, and–less frequently– swelling, burning, and stinging.[nationaleczema.org]
  • In milder cases, the rebound eruption simply consists of flushing or erythema with or without exudative edema, while in the more severe cases, a myriad of skin manifestations, including papules, pustules, or erosions ( Figure 2 ), can be seen.[dovepress.com]
Emotional Lability
  • Specifically, the clinical picture may include malaise, weakness, lethargy, hyposthenia, nausea, emesis, anorexia, weight loss, diffuse headaches, postural hypotension, myalgia, arthralgia, mood changes, and emotional lability.[symptoma.com]

Workup

When evaluating cases presenting with the above non-specific symptoms, it is imperative to elicit the medication list including the duration, frequency, dose, and last use of all drugs. In addition, the patient's complete medical history and physical exam are key components of the workup. Very importantly, the diagnosis of steroid withdrawal syndrome should be confirmed through the appropriate studies that test the integrity of the HPA axis [5].

Laboratory tests

The clinician should differentiate glucocorticoid therapy withdrawal from other cause of adrenal insufficiency [5]. This can be achieved by obtaining the measurement of the 9 am cortisol levels [9]. Note that a cortisol value below 100nmol/l is indicative of cortisol insufficiency while levels above 450nmol/l are likely normal [10].

Those with a level between 100nmol/l and 449nmol/l warrant further testing with stimulation tests [5]. These include the short Synacthen test (SST) (a synthetic ACTH), glucagon stimulation test (GST), and insulin tolerance test (ITT), and others that are not commonly used [5]. These will examine various components of the HPA axis. Note that GST and ITT are more invasive. Additionally, the SST demonstrates sensitivity and specificity for adrenal insufficiency.

Other pertinent studies include a complete blood count (CBC), electrolyte panel and serum calcium, renal function test, and thyroid function tests. A fever workup should also be done which should include blood and urine cultures, as well as chest X-ray [1].

Imaging

Other than chest radiography, computed tomography (CT) scan of the adrenals and head scan can be performed to rule out other causes of adrenal insufficiency.

Other

An electrocardiograph (ECG) should be obtained in medical emergencies.

Abnormal Thyroid Function Test
  • THYROID FUNCTION TEST 47 THYROID DISORDERS OF INFANCY 462 P A RT IV CALCIUM AND BONE METABOLISM 473 MORPHOLOGY OF THE PARATHYROID 51 PARATHYROID HORMONE 497 PHYSIOLOGY OF CALCIUM 52 PARATHYROID HORMONERELATED 512 CLINICAL APPLICATION OF BONE MINERAL[books.google.de]

Treatment

  • Good to know If you have gone through long-term cortisone treatment and you feel anxious/nervous or depressed after stopping treatment, please contact your doctor.[cortisone-info.com]
  • Although the duration of steroid administration is short, Steroid Withdrawal Syndrome (SWS) has been documented after treatment.[jlc.jst.go.jp]
  • However, lower potency steroids can still cause adverse effects on the skin and therefore also should not be used as a daily, long-term treatment.[epiphanytherapeutics.com]
  • It is generally regarded that a topical steroid is a safe treatment option both in short-term daily use and the long-term intermittent use.[drwangskincare.com]
  • […] steroid withdrawal syndrome and performance status (according to Lansky scale) during the 9-day tapering period and 1 week after withdrawal of the steroid in 63 children randomly allocated to receive prednisone or dexamethasone as part of induction treatment[ncbi.nlm.nih.gov]

Prognosis

  • What is the prognosis of steroid withdrawal? The prognosis of steroid withdrawal, if quickly recognized and treated, is usually good.[rxlist.com]
  • Neuroradiology 42(2): 112–4 PubMed CrossRef Google Scholar Yu C, Sharma N, Saab S (2013) Hyponatremia: clinical associations, prognosis, and treatment in cirrhosis.[link.springer.com]

Etiology

  • The Steroid Withdrawal Syndrome: A Review of the Implications, Etiology, and Treatments. Journal of Pain and Symptom Management. 2007; 33(2): 224-228. Popular T hreads Discussing Prednisone Withdrawal[crohnsforum.com]
  • There are several theories in the literature regarding the mechanism and etiology of steroid withdrawal syndrome. One theory attributes the symptoms to an adaptive increased tissue demand for steroids that develops while they are being used.[clinicaladvisor.com]
  • If a certain condition will improve with the use of cortisone, then somewhere in its etiology must be an adrenal weakness".[cssassociation.org]
  • AIDS: etiology, diagnosis, treatment and prevention update. Philadelphia: Lippincott, 1993;6:1–13. 15. Gagnon S, Boota AM, Fischi MA, et al.[aafp.org]

Epidemiology

  • Data on epidemiology, likely causal agents, complementary tests, concomitant pathologies, management, evolution and complications was gathered through a retrospective study. Results. Thirteen patients were included, with a mean age of 53 years.[actasdermo.org]
Sex distribution
Age distribution

Pathophysiology

  • Bacterial meningitis: recent advances in pathophysiology and treatment. Ann Intern Med . 1990;112:610–23. 47. Quagliarello V, Scheld WM. Bacterial meningitis: pathogenesis, pathophysiology, and progress. N Engl J Med . 1992;327:864–72. 48.[aafp.org]

Prevention

  • A gradual decrease in dosage could help prevent this phenomenon. Good to know If you have gone through long-term cortisone treatment and you feel anxious/nervous or depressed after stopping treatment, please contact your doctor.[cortisone-info.com]
  • The syndrome may be prevented by gradual rather than abrupt withdrawal of corticosteroid therapy.[medical-dictionary.thefreedictionary.com]
  • A very important consideration for individuals who have completed treatment is that exogenous glucocorticoids should be gradually and slowly tapered off to prevent adrenal insufficiency and its sequelae.[symptoma.com]
  • Is it possible to prevent steroid withdrawal? Yes, it is possible to prevent steroid withdrawal. The best way to prevent steroid withdrawal is to be sure to use steroids conservatively and for the shortest period possible.[rxlist.com]
  • Be familiar with the different prednisone withdrawal symptoms to prevent further problems.[drugsdb.com]

References

Article

  1. Margolin L, Cope DK, Bakst-Sisser R, Greenspan J. The steroid withdrawal syndrome: a review of the implications, etiology, and treatments. J Pain Symptom Manage. 2007;33(2):224-228.
  2. Hochberg Z, Pacak K, Chrousos GP. Endocrine withdrawal syndromes. Endocr Rev. 2003;24(4):523-538.
  3. Kirwan JR. Systemic corticosteroids in rheumatology. In: Hochberg MC, Silman AJ, Smolen JS, eds. Rheumatology. 3rd ed. St. Louis, MO: Mosby; 2003:385.
  4. Bhattacharyya A, Kaushal K, Tymms DJ, Davis JR. Steroid withdrawal syndrome after successful treatment of Cushing’s syndrome: a reminder. Eur J Endocrinol. 2005;153(2):207-210.
  5. Iliopoulou A, Abbas A, Murray R. How to manage withdrawal of glucocorticoid therapy. Prescriber. 2013;24(10)23-29.
  6. Amatruda TT, Hurst MM, D'esopo ND. Certain endocrine and metabolic facets of the steroid withdrawal syndrome. J Clin Endocrinol Metab. 1965;25(9):1207–1217.
  7. Saracco P, Bertorello N, Faarinasso L, et al. Steroid withdrawal syndrome during steroid tapering in childhood acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2005; 27(3):141–144.
  8. Henneman PH, Wang DM, Irwin JW, Burrage WS. Syndrome following abrupt cessation of prolonged cortisone therapy. J Am Med Assoc.1955;158(5):384–386.
  9. Byyny RL. Withdrawal from glucocorticoid therapy. N Engl J Med. 1976;295(1):30–2.
  10. Courtney CH, McAllister AS, McCance DR, et al. Comparison of one week 0900 h serum cortisol, low and standard dose synacthen tests with a 4 to 6 week insulin hypoglycaemia test after pituitary surgery in assessing HPA axis. Clin Endocrinol (Oxf). 2000;53(4):431–436.

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Last updated: 2018-06-21 20:15