Schmidt’s Syndrome Presenting as Diabetic Ketoacidosis and Adrenal Crisis: A Case Report and Review of Literature

Introduction: Schmidt’s Syndrome, is a rare endocrine disorder defined by the combined occurrence of Addison disease, autoimmune thyroid disease, and type 1 diabetes mellitus. The rarity of the condition and the presentation of adrenal insufficiency and hypothyroidism often lead to misdiagnosis with life-threatening consequences for the patients. We report a case presenting with adrenal insufficiency and diabetic ketoacidosis who was diagnosed with Schmidt’s Syndrome. Case Description: We describe the case of a 38-year-old male with a past medical history of hypothyroidism, who was admitted for worsening abdominal pain, nausea, vomiting, fevers, and chills. Physical exam revealed underweight male with marked dehydration, diaphoresis, in moderate abdominal pain. Initial vital signs and laboratory panel raised suspicion for adrenal insufficiency and diabetic ketoacidosis. Blood pressure 82/42mmHg, HR of 121, sodium 128mmol/L, potassium 6.8mmol/L, chloride 104mmol/L, bicarbonate 5mmol/L, BUN 20mg/dl, Creatinine 1.5mg/dl, Glucose 402mg/dl, TSH 60, and serum osmolality 319mosm/kg. The electrolyte derangements and vital signs improved after the initiation of the high-dose steroids and insulin. The patient was transitioned to a regimen of hydrocortisone/ fludrocortisone, levothyroxine, and insulin basal/bolus and was discharged in clinically stable conditions to follow up with an endocrinologist. Discussion: The prevalence of Schmidt’s syndrome is 1:20,000 in the general population and a 3:1 ratio of females to males. Autoimmune thyroid disease is present in 70–75%, T1DM in 40–60%, and Addison’s disease in 40–50%. This syndrome can be associated with other non-endocrine autoimmune disorders, such as vitiligo, myasthenia gravis, Sjogren’s syndrome, rheumatoid arthritis, and primary antiphospholipid syndrome. The initial step in diagnosis should be checking serum morning cortisol levels to identify adrenal insufficiency. Autoimmune antibodies play an important role to confirm the diagnosis including 21-hydroxylase, 17-hydroxylase, thyroid peroxidase, glutamic acid decarboxylase, islet cells, anti-tissue transglutaminase antibodies, parietal cell, and anti-intrinsic factor antibodies. Currently, treatment is limited to hormone replacement in patients with organ failure. But it is crucial to replace corticosteroids before starting thyroid replacement in patients with adrenal insufficiency. Conclusion: A high level of diagnostic suspicion is required for the diagnosis of Schmidt’s syndrome when encountering a patient with autoimmune disease. The diagnosis of this syndrome is often delayed, causing adverse events. With this case presentation, we add to the data pool of Schmidt’s syndrome with the ability to significantly improve patients outcomes with early diagnosis and hormone replacement.

Features of clinical manifestations and treatment of Schmidt’s syndrome

Background. Autoimmune polyglandular syndrome type 2 is the most common. The development and course of Schmidt’s syndrome is of interest, which requires a comprehensive diagnosis due to the combination of several autoimmune endocrinopathies, and rational therapy. The purpose of this work was to analyze the features of clinical manifestations and treatment of autoimmune polyglandular syndrome type 2 using a specific example. Materials and methods. A clinical case of Schmidt’s syndrome in a 36-year-old female patient is presented for consideration. There were primary adrenal insufficiency with an autoimmune process to 21-hydroxylase and the presence of autoimmune thyroiditis with the development of hypothyroidism. Results. The clinical manifestations of the disease were mainly represented by syndromes of hypotension, general and muscle weakness, hyperpigmentation, weight loss, dyspeptic disorders, aggravated by secondary viral infection, against the background of edematous syndrome. Additional examination revealed a significant increase in adrenocorticotropic hormone, renin, hyperkalemia, hypercholesterolemia, increased 17-hydroxyprogesterone, thyroid-stimulating hormone, hypothyroxinemia, an increase in antibodies to 21-hydroxylase and thyroid peroxidase and a decrease in the thyroid volume with multiple linear inclusions, increased echogenicity. The analysis of the identified hormonal, metabolic and pathomorphological changes made it possible to establish the pre­sence of Schmidt’s syndrome in this clinical case. The treatment with glucocorticoids was accompanied by adverse reactions, which led to repeated replacement of drugs. The choice was made in favor of сortef, the dose was carefully titrated under the control of cortisoluria. The administration of levothyroxine was accompanied by the achievement of euthyroidism. Conclusions. The symptoms of Schmidt’s syndrome with the simultaneous manifestation of primary adrenal insufficiency of autoimmune origin and autoimmune thyroiditis with the deve­lopment of hypothyroidism differed in terms of a mutually aggravating course. There were significant difficulties in the treatment of this polyglandular syndrome associated with the correction of hypocorticism due to poor tolerance of glucocorticoids, which required constant monitoring, continuous control of the hormonal and metabolic status.

SAT-230 Newly Diagnosed Schmidt’s Syndrome and Steroid Induced Psychosis

In 1926, Schmidt reported the combination of hypothyroidism and adrenal insufficiency (AI) with lymphocytic infiltration of both the thyroid and adrenal glands.1 This syndrome is now known as autoimmune polyendocrine syndrome (APS) type 2, characterized by two of the following three endocrinopathies: type 1 diabetes, autoimmune thyroiditis, and Addison’s disease.2 It may seem surprising that transient relative hypercortisolemia in AI patients at the beginning of treatment results in steroid induced psychosis (SIP). Here, we present a patient who developed SIP after starting steroid for AI. 44 year old Caucasian female with bipolar disorder and Hashimoto’s thyroiditis was admitted for generalized weakness, nausea, vomiting and weight loss of about 15 pounds in 3 months. On exam, blood pressure was 93/54 mmHg and pulse rate was 99. Her abdomen and arms looked hyperpigmented. Lab test revealed plasma glucose of 68 mg/dl, serum sodium of 129 mmol/l (133-145), potassium of 4.9 mmol/l (3.6 – 5.2), bicarbonate of 20 mmol/l (22 – 29). TSH was 16.93 mIU/ml (0.4 – 4.00) and FT4 was 0.74 ng/dl (0.7 1.8). CT abdomen and pelvis with contrast was unremarkable. As AI was suspected, cortisol level was checked and low at 0.5ug/dl. Cosyntropin stimulation test (CST) revealed pre-CST cortisol of 0.4 ug/dl, and post CST cortisol of 0.5 ug/dl at 45 min. ACTH was elevated at 514.4 pg/ml (7.2 – 63.3). A diagnosis of Schmidt’s syndrome was made based on elevated 21 hydroxylase of 8.5 U/ml (<1.0) and anti-thyroid peroxidase antibody of 20.5IU/ml (<5.6). Screening for type 1 diabetes and celiac disease was negative. After CST, stress dose hydrocortisone was started and dose was gradually tapered down in a few days. However, five days after steroid therapy, patient was admitted for suicidal ideation and catatonia which resolved quickly with Ativan and steroid taper to physiologic dose. APS type 2 has a prevalence of 1:1000. Clinicians should raise the suspicion for this syndrome in the appropriate context as seen in this patient presenting with classic features of AI. Although SIP in AI patients is not frequently reported, we should be mindful about this potential event especially in patients with underlying psychiatric illness. It is postulated that prolonged hypocortisolism in undiagnosed AI might lead to upregulation of central glucocorticoid receptors and hence glucocorticoid replacement might elicit a relative supraphysiological response in these patients.3

Jaundice and anaemia as presenting features of an incomplete autoimmune polyglandular syndrome type II

The coexistence of adrenal failure with either autoimmune thyroid disease and/or type 1 diabetes is defined as autoimmune polyglandular syndrome (APS) type 2 or Schmidt’s syndrome. Vitiligo, hypergonadotropic hypogonadism, chronic autoimmune hepatitis, alopecia, pernicious anaemia and seronegative arthritis may also be present. We present a case of 45-year-old Indian man with progressive jaundice and asthenia for 3 months. He was also found to have pallor, icterus, dry coarse skin and delayed relaxation of ankle jerk. Investigations showed pancytopaenia with megaloblastic changes due to pernicious anaemia, autoimmune hypothyroidism and autoimmune adrenalitis with evolving adrenal insufficiency. Upper gastrointestinal endoscopy guided biopsy showed evidence of gastric mucosal atrophy. Patient responded well to hydroxocobalamin and thyroxine replacement. Detailed workup to check for evolving APS II is prudent in a hypothyroid patient presenting with pallor and jaundice. It may alert physicians to possible adrenal crisis in the future, especially after starting levothyroxine replacement in these patients.

Combined atypical primary hypoadrenocorticism and primary hypothyroidism in a dog

A dog with combined atypical primary hypoadrenocorticism and primary hypothyroidism is described. The dog presented with waxing and waning, vague complaints since more than a year and had been treated with several drugs without complete resolution of signs. Based on the abnormalities on physical examination, blood examination and abdominal ultrasonography, atypical primary hypoadrenocorticism and primary hypothyroidism were diagnosed. Glucocorticoid supplementation was started and gradually tapered to maintenance rate because of polydipsia. Ten days later, levothyroxine supplementation was started at a very low dose and was gradually increased based on serum total thyroxine concentrations. The dog rapidly improved and recovered completely. Follow-up over a one-year period did not reveal new abnormalities. The presence of combined primary hypoadrenocorticism and primary hypothyroidism has been infrequently described in dogs and may resemble the Schmidt’s syndrome in humans.