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Year : 2015  |  Volume : 12  |  Issue : 3  |  Page : 116-118

Levothyroxine replacement before glucocorticoid replacement leading to adrenal crisis in a case of autoimmune polyendocrine syndrome type II (Schmidt syndrome)

Department of Endocrinology, Sir Ganga Ram Hospital, New Delhi, India

Date of Web Publication16-Oct-2015

Correspondence Address:
Dr. Om J Lakhani
Room - 1407, Endocrinology Office, 4th Floor, Sir Ganga Ram Hospital, New Delhi - 110 060
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-0354.157932

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Autoimmune polyendocrine syndrome II (APS II) is defined as Primary adrenal insufficiency with Autoimmune hypothyroidism and/or Type 1 Diabetes. Hypothyroidism is commonly diagnosed but adrenal insufficiency often gets missed out. Levothyroxine replacement before glucocorticoid replacement in a patient APS II can lead to precipitation of adrenal crisis. We report a case of Autoimmune polyendocrine syndrome type II (Schmidt syndrome) who presented to us in adrenal crisis after having started on Levothyroxine without glucocorticoid replacement.

Keywords: Autoimmune polyendocrine syndrome II, addison′s disease, autoimmune polyendocrine syndrome II, adrenal crisis, autoimmune hypothyroidism, levothyroxine, primary adrenal insufficiency, schmidt syndrome

How to cite this article:
Lakhani OJ, Tripathi S, Indu K C, Desai M. Levothyroxine replacement before glucocorticoid replacement leading to adrenal crisis in a case of autoimmune polyendocrine syndrome type II (Schmidt syndrome). Thyroid Res Pract 2015;12:116-8

How to cite this URL:
Lakhani OJ, Tripathi S, Indu K C, Desai M. Levothyroxine replacement before glucocorticoid replacement leading to adrenal crisis in a case of autoimmune polyendocrine syndrome type II (Schmidt syndrome). Thyroid Res Pract [serial online] 2015 [cited 2022 Dec 4];12:116-8. Available from: https://www.thetrp.net/text.asp?2015/12/3/116/157932

  Introduction Top

Autoimmune polyendocrine syndrome II (APS II) is defined as Primary adrenal insufficiency with Autoimmune hypothyroidism and/or Type 1 Diabetes mellitus (T1DM). Primary adrenal insufficiency with Autoimmune hypothyroidism is also known as Schmidt syndrome. [1] Here we report a case of a young male diagnosed to having APS II in whom the component of autoimmune hypothyroidism was easily diagnosed but a more classical primary adrenal insufficiency was missed out. In coexisting primary adrenal insufficiency and Hypothyroidism if levothyroxine is replaced before glucocorticoid, it leads to increased cortisol clearance precipitating an adrenal crisis. [2] The patient was started on Levothyroxine replacement without hydrocortisone replacement which led to the patient presenting in adrenal crisis. The case illustrates the need to keep a high index of suspicion in diagnosing primary adrenal insufficiency in case of autoimmune hypothyroidism and replacing glucocorticoids before levothyroxine.

  Case Report Top

A 22-year-old male had history of significant weight loss (about 15-18 kg), generalized fatigue and darkening or skin and oral mucosa over a period of 1 year [Figure 1] and [Figure 2]. Prior to admission at our hospital, patient was admitted thrice in the span of one year, each time with vomiting and diarrhea and was found to have hypotension. In the third admission the patient was suspected to have some thyroid disorder and a thyroid function test was done. Patient was found to have overt hypothyroidism and started on levothyroxine on discharge. After taking the medication the patient felt worse and developed syncope and hypotension for which he reported to the emergency department at our institute. On evaluation of the patient, we found that the patient had a classical textbook picture of primary adrenal insufficiency and was in state of adrenal crisis.
Figure 1: Skin hyperpigmentation in patient with APS II

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Figure 2: Gum hyperpigmentation in patient with APS II

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On clinical evaluation after admission patient was found to have a supine blood pressure of 90/60 mmHg. He was found to have dark pigmentation of gums, tongue and oral mucosa [Figure 2]. Dark pigmentation was also found over knuckles, palmar creases, shin and over the foot [Figure 1]. Patient had no features of hypogonadism, vitiligo or hair loss.

On investigations patient was found to have hyponatremia, hyperkalemia and metabolic acidosis. Based on a clinical suspicion of Addison's disease a Serum cortisol and Serum ACTH was ordered and an intramuscular ACTH stimulation test (25 IU of Acton Prolongatum ® ) was done which confirmed the diagnosis of Addison's disease [Table 1]. Patient was found to have primary hypothyroidism on thyroid function test with positive thyroid peroxidase antibody confirming the autoimmune nature of the thyroid disease. A screen for other autoimmune disease like, T1DM (Blood sugars, HbA1c and GAD65 antibodies), primary hypogonadism (with total testosterone), celiac disease (with IgA anti Tissue transglutaminase) and pernicious anemia (Vitamin B12) did not reveal anything significant. Chest X-ray did not show signs of tuberculosis and HIV was negative. The patient was diagnosed to have autoimmune polyendocrine syndrome type II based on primary adrenal insufficiency and autoimmune hypothyroidism also known as Schmidt syndrome.
Table 1: Relevant investigation findings (original table)

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Patient was initially treated with injectable hydrocortisone and fludrocortisone along with other supportive medications and IV fluids. Thyroid replacement was started with levothyroxine in dose of 75 µg once glucocorticoids were replaced. Patient responded with correction of the electrolyte imbalance, normalization of the blood pressure and improvement in general wellbeing. Patient was discharged on oral hydrocortisone in dose of 10 mg at 8 am, 5 mg at 12 noon and 5 mg at 5 pm along with fludrocortisone and levothyroxine. Patient was advised to double the dose of the hydrocortisone in case of intercurrent illness or stress.

  Discussion Top

Autoimmune polyendocrine syndromes are autoimmune disorders involving 2 or more endocrine glands. It is classified into four types based on Neufeld and Blizzard classification [Table 2]. [3]
Table 2: Neufeld and blizzard classification of autoimmune polyendocrine syndrome

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APS type II is more common than type I and seen in adulthood. It is associated with primary adrenal insufficiency along with autoimmune thyroid disease and/or T1DM. The syndrome of primary adrenal insufficiency with autoimmune hypothyroidism is also called Schmidt syndrome and presence of additional T1DM is called as Carpenter's syndrome. It is associated with HLA class II and has autosomal dominant form of inheritance. Hypogonadism, pernicious anemia and host of other autoimmune disease may be associated with APS II. Adrenal insufficiency is associated with Anti-21 α hydroxylase antibody and autoimmune hypothyroidism is associated with anti-thyroid peroxidase (TPO) and/or anti-thyroglobulin (Tg) antibody. [1]

In case of combined adrenal insufficiency and hypothyroidism, adrenal insufficiency is generally treated first. This is because giving thyroxine first can enhance cortisol clearance and precipitate an adrenal crisis. [2] Fonseca et al., have opined that levothyroxine when given to patient with hypothyroidism increases the basal metabolic rate (BMR) leading to increased requirement of cortisol, which if no met can precipitate an adrenal crisis. [4]

Mainstay of treatment of chronic adrenal insufficiency is with oral hydrocortisone with fludrocortisone. The starting dose of hydrocortisone in adults is 20-30 mg/day given in dose dose given in 2 or 3 divided doses. Hydrocortisone is preferred over longer acting glucocorticoids like prednisolone and dexamethasone. Patient with adrenal insufficiency are advised to double the dose of medication in case of intercurrent illness. Medical alert bracelets are often prescribed to such patients. [5]

  References Top

McLaren N. Autoimmune Polyglandular Syndromes. In: Jameson JL, Groot LD, editors. Endocrinology Adult and Pediatric. Saunders Elsevier; 2010. p. 2702-10.  Back to cited text no. 1
Arlt W, Allolio B. Adrenal insufficiency. Lancet 2003;361:1881-93.  Back to cited text no. 2
Neufeld M, Blizzard RM. Polyglandular autoimmune disease. In: Pinchera A, Doniach D, Fenzi DF, Baschieri L, editors. Autoimmune Aspects of Endocrine Disorders. London: Academic Press; 1980:357-65.  Back to cited text no. 3
Fonseca V, Brown R, Hochhauser D, Ginsburg J, Havard CW. Acute adrenal crisis precipitated by thyroxine. Br Med J (Clin Res Ed) 1986;292:1185-6.  Back to cited text no. 4
Oelkers W. Adrenal insufficiency. N Engl J Med 1996;335:1206-12.  Back to cited text no. 5


  [Figure 1], [Figure 2]

  [Table 1], [Table 2]

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