EmDOCs Podcast – Episode 19: Decompensated Hypothyroidism and Euglycemic Diabetic Ketoacidosis

Today on the emDocs cast with Brit Long, MD (@long_brit) we cover two topics: Decompensated Hypothyroidism and Euglycemic Diabetic Ketoacidosis.

Part 1: Decompensated Hypothyroidism

Hypothyroidism diabetic coma

– Decompensated hypothyroidism, AKA Myxedema Coma, is a diagnosis we must recognize early in the ED as delayed or missed diagnosis carries significant mortality and morbidity. Unfortunately, it can be difficult to diagnose with its nonspecific symptoms.

– Classic picture is an elderly female patient in winter months who is altered and hypothermic.

– Variety of precipitating causes: Infection/sepsis (most common cause), environmental exposure (cold), hypoglycemia, PE, CHF, stroke, intoxication, MI, burn, trauma, anemia, medications (noncompliance, amiodarone, beta blockers, sedatives, opioids, lithium, phenytoin)

– Presentation:

  • Altered Mental Status: Myxedema coma is a misnomer. These patients typically don’t present in true coma, but rather with altered mental status or confusion.
  • Low and Slow: Hypothermic, bradycardic, hypotensive, hypoxemic, hypercapnic, and hypoglycemic. Hypothermia is extremely common in decompensated hypothyroidism. A normal temperature in a decompensated hypothyroid patient is concerning for underlying infection.
  • Precipitating event: Must treat underlying etiology/precipitating cause (ie, infection needs antibiotics).
  • History of hypothyroidism: Look for anterior midline neck scar, history of radioactive iodine ablation, or levothyroxine on the medication list.

– Obtain ECG, CXR, renal and liver function, electrolytes, CBC, CK, coagulation panel, VBG, UA. Due to AMS, head CT is likely recommended. May find hyponatremia, hyperkalemia, elevated liver enzymes, elevated CK, AKI, coagulopathy. ECG may show bradycardia, low voltage, QT prolongation.

– Treatment: Priorities include airway, hemodynamics, managing underlying etiology, steroids and thyroid hormone administration, supportive care.

  • Airway: difficult airway due to lingual edema and physiologic derangements.
  • Resuscitate with fluids and vasopressors, though patients often do not improve until they receive steroids and thyroid hormone.
  • Replete glucose.
  • Broad-spectrum antibiotics recommended.
  • Passive rewarming.
  • IV steroids to include hydrocortisone and IV thyroxine (T4) at 4 mcg/kg, or 100-500 mcg IV. T3 is controversial but can be considered in those who do not respond to T4 or those who are critically ill; however, it increases risk of arrhythmia.

– How often do we miss it? Studies suggest only 21% of primary overt hypothyroidism is diagnosed in the ED, with median time to diagnosis being 3 days. Of patients found to be in decompensated hypothyroidism only 50% were initially diagnosed in the ED. Mortality can reach 100% if not treated.

– Why do we miss it? Ambiguity and nonspecific symptoms. The precipitating cause may explain the patient’s presentation and signs/symptoms, and clinicians may anchor on this.

– How do we improve? Decompensated hypothyroidism is a clinical diagnosis, not based on labs (though they can assist us). Consider the condition in those with the ‘low and slow’ features,  those with multiple non-specific complaints, those who fail to respond to vasopressors and fluids, and repeat episodes of hypoglycemia.

Part 2: Euglycemic DKA

Hypothyroidism diabetic coma


Diabetic ketoacidosis (DKA) is an endocrine emergency. A subset of diabetic patients may present with relative euglycemia with acidosis, known as euglycemic diabetic ketoacidosis (EDKA), which is often misdiagnosed due to a serum glucose < 250 mg/dL.

– EDKA was first described in 1973 by Munro et al., followed by the publication of a larger case series in 1993. The recognition and incidence of EDKA have increased in recent years, specifically with sodium-glucose cotransporter-2 (SGLT2) inhibitors in insulin-deficient patients with chronic type 2 diabetes, type 1 diabetes, or latent autoimmune diabetes.


Complex pathophysiology, which likely includes an absolute insulin deficiency or relative insulin deficiency with severe insulin resistance. This leads to increased glucagon and fatty acid release.

– Mechanism also includes reduced glucose availability and production during a fasting state and/or increased urinary glucose excretion.

– SGTL2 inhibitors work on the sodium-glucose cotransporter-2 protein, which is located in the proximal renal tubules and responsible for absorption of up to 90% of filtered glucose. This increases urinary excretion and blocks the reabsorption of glucose, resulting in glucosuria, reduced serum availability of carbohydrates, and volume depletion.

– Wide variety of conditions associated with EDKA, including fasting state, gastroparesis, renal disease, liver disease, intoxication, pregnancy, infection, SGLT2 inhibitor use, self-treatment with insulin for DKA prior to ED presentation.


– Close to 50% of patients experience a delay in diagnosis due to relatively normal glucose values.

– Symptoms include nausea, vomiting, malaise, and fatigue. Vomiting may be one of the most common findings.


– Beta-hydroxybutyrate and pH recommended by the American College of Endocrinology for diagnosis.

– Consider obtaining electrolytes, glucose, renal function, serum ketones, and a venous blood gas.

Hypothyroidism diabetic coma


– Balanced crystalloid fluid resuscitation with 1-2 L during the first 1-2 hours.

– For patients with serum potassium between 3.5-5.5 mEq/L, initiate insulin at a rate of 0.05-0.1 units/kilogram/hour alongside dextrose 5% to avoid hypoglycemia and improve resolution of ketosis.

Read more  Case Report: Occurrence of Thyroid Storm in a Young Patient With Recurrent Diabetic Ketoacidosis

– Insulin is utilized to resolve ketoacidosis, no matter the serum glucose level, and insulin infusion is recommended even if patients do not use insulin for home serum glucose control.

– Monitor glucose and serum electrolytes every hour. SGLT2 inhibitors should be discontinued, but they may be restarted after resolution of EDKA. Due to need for monitoring and insulin infusion, admission to the ICU is likely needed.


– Clinicians should consider EDKA in patients with nausea, vomiting, malaise, or fatigue in those with chronic liver disease, starvation, pregnancy, or on SGLT2 inhibitor.

– A glucose < 250 mg/dL should not be used to exclude DKA.

– If EDKA is possible, serum pH, bicarbonate, and ketones should be obtained.

– Treatment includes intravenous fluids, insulin, and glucose, as well as management of the underlying etiology (ie, antibiotics for infection).

— Update: 04-01-2023 — cohaitungchi.com found an additional article Case Report: Occurrence of Thyroid Storm in a Young Patient With Recurrent Diabetic Ketoacidosis from the website www.frontiersin.org for the keyword hypothyroidism diabetic coma.


Thyroid storm (TS) is a life-threatening endocrine emergency that leads to multiple organ dysfunction. The incidence of TS in Japan is 0.2 per 100,000 population per year (1). Undiagnosed and untreated TS in the late stages can be associated with high mortality (2, 3). Women are more likely to develop TS, which can occur at any age (4). TS usually results from precipitating events such as surgery, sepsis, burn injury, diabetic ketoacidosis (DKA), cardiovascular accidents, parturition, status epilepticus, I131 treatment, and iodinated contrast dyes (5).

DKA is a serious complication of a disordered metabolic state, characterised by hyperglycaemia, ketosis, and metabolic acidosis (6). The annual incidence of DKA is 0–56 per 1000 population per year (7). Women have a higher prevalence of DKA than men (7), and those aged 18–44 years are more likely to develop DKA than other age groups (8).

Previous reports have confirmed the co-occurrence of DKA and thyroid crisis. However, owing to its rarity, its clinical course remains unclear (9, 10). In this study, we present a rare case of TS in a young man with recurrent DKA.

Case Description

Ethics Consideration and Patient Details

This case study was conducted according to the CARE guidelines (11). Written informed consent was obtained from the patient for the publication of this case report and accompanying images.

A 25-year-old man who had a history of type 1 diabetes mellitus and was on insulin therapy was brought to the emergency room for disturbance in consciousness and nausea. The patient had been frequently admitted to the hospital for similar symptoms in the past few months and had a diagnosis of DKA because he had poor adherence to insulin therapy. He had a medical history of Graves’ disease since he was 15 years old. Methimazole and potassium iodide were used for the treatment. He frequently stopped going to the hospital at his own discretion. When the patient was admitted to the hospital for the aforementioned symptoms, 2 months had passed since his last discharge from the hospital.

Clinical Finding

On admission, his vital signs were as follows: blood pressure, 130/64 mmHg; pulse rate, 220 beats per minute (atrial fibrillation); respiratory rate, 40 breaths per minute, O2 saturation, 99% on room air; body temperature, 36.3°C; E2, V3, M5, and a total of 10 points on the Glasgow Coma Scale. Results of blood gas analysis showed a pH of 7.036, glucose level of 736 mg/dL, base excess of -24.4 mmol/L, lactate level of 26.0 mg/dL, HCO3− of 6.3 mmol/L, anion gap of 27.5 mmol/L, Na+ level of 125.6 mmol/L, K+ level of 5.15 mmol/L, and increased production of urine ketone body. The HbA1c level at the ICU admission was 12.2%. Considering the metabolic acidosis, hyperglycaemia, and the patient’s medical history, his condition was diagnosed as DKA, and he was therefore admitted to the intensive care unit.

Treatment and Outcomes

Rapid administration of extracellular fluid to replenish intravascular volume, continuous administration of fast-acting insulin to manage hyperglycaemia, and correction of electrolyte abnormalities were performed, but he showed poor improvement in consciousness level.

Because of the prolonged disturbance of consciousness, a thorough examination was performed for a suspected diagnosis of thyrotoxicosis. Results of laboratory blood testing using electrochemiluminescent immunoassay revealed the presence of thyrotoxicosis, with the following clinical findings: thyroid-stimulating hormone, 0.005 μIU/mL [normal range: 0.50 – 5.0 μIU/mL]; free T3, 21 pg/mL [normal range: 2.3 – 4.0 pg/mL]; free T4, 6.7 ng/dL [normal range: 0.9 – 1.7 ng/dL].

In addition to the restlessness symptoms associated with the central nervous system, tachycardia, nausea, and congestive heart failure were observed, which are symptoms of TS. The patient’s medical history showed poor adherence with treatment for Graves’ disease, which also contributed to a suspicion of TS. Based on the Burch–Wartofsky Point Scale for TS (12), the patient’s score was 80, which was considered highly suggestive of TS. Based on the Japan Thyroid Association criteria (2), TS was diagnosed.

Read more  Endocrine Society of India management guidelines for patients with thyroid nodules: A position statement : Indian Journal of Endocrinology and Metabolism

Antithyroid medication, inorganic iodine, and corticosteroids were promptly started as treatment for TS, and beta-blockers were administered for managing tachycardia. TS treatment was successful, and the patient’s consciousness disorder and tachycardia improved. DKA also improved without complications of other organ damage, and the patient was discharged to the general ward on the third day after admission to the intensive care unit. The patient was discharged on the tenth day of hospitalisation and continues to receive outpatient treatment. Progression of TSH, free T4, and free T3 during the clinical course is shown in Table 1.


This case reveals the clinical course of TS that developed during the follow-up of repeated DKA.

The occurrence of TS and DKA can be concurrent, which is rare but a life-threatening emergency presentation. A previous report showed that the mortality rate of the concurrent presentation of TS and DKA was 15% (13). While the mortality rate is high, the concurrent presentation of the two endocrine disorders, namely, DKA and TS, is very rare. Several factors could mask or delay early diagnosis. Therefore, the simultaneous presentation of these two endocrine emergencies poses a diagnostic challenge.

In this case, it was difficult to make a diagnosis of TS at the time of initial examination because the patient had a history of recurrent DKA, and the symptoms at the time of presentation were consistent with DKA. The symptoms associated with the central nervous system did not improve after initiating treatment for DKA, and because the patient had severe tachycardia and a history of hyperthyroidism, blood tests for assessing thyroid function were performed; these results led to the diagnosis of TS. TS could thus be diagnosed relatively early and early treatment could be started—one of the reasons the patient’s life could be saved.

Thyroid function and glucose metabolism are closely related, and normal thyroid function is essential for maintaining equilibrium in glucose metabolism. However, excess levels of thyroid hormones have been implicated to be responsible for increased intestinal glucose absorption, increased hepatic production of glucose from glycogen, decreased insulin secretion from the pancreas, increased insulin resistance, and increased renal clearance of insulin. A previous study showed that hyperthyroidism worsened glycemic control in patients with diabetes (14). Additionally, both TS and DKA have similar predispositions (15, 16), and they are likely caused by a common trigger. A previous report showed that an initial trigger by excessive levels of thyroid hormones causes DKA, which subsequently leads to TS (17). The coexistence of diabetes mellitus with hyperthyroidism is a known clinical observation and hyperthyroidism aggravates glucose intolerance multiple mechanisms (18). A recent review shows that efforts should be made to maximize patient adherence to antithyroid and anti-diabetic agents when treating patients with the simultaneous development of TS and DKA (13). Another recent review demonstrates the importance of being aware of the possible simultaneous development of DKA and TS in patients with a history of Graves’ disease (19). In this case, the patient’s compliance with medication was poor, and inadequate antithyroid medication may have resulted in excess production of thyroid hormones, resulting in DKA and subsequent concurrent TS.

Based on our case findings, we suggest the following learning points. First, there needs to be awareness that DKA can precipitate TS. Second, if a patient with DKA presents with persistent tachycardia and disturbance of consciousness, TS should be considered in the differential diagnosis. Third, if the thyroid function tests revealed the diagnosis of thyroid crisis, the physician should start the management with antithyroid drugs, insulin and intravenous fluids.


The simultaneous presentation of TS and DKA is rare, but it can be life-threatening if diagnosis and treatment are delayed. A comprehensive clinical evaluation, including physical examination and laboratory investigations, will be needed for the early detection of these rare presentations. We also need to pay close attention to the patient’s previous medication compliance to prevent deterioration of the concurrent presentation. These approaches could help clinicians in the early detection and multidisciplinary treatment of patients with concurrent TS and DKA.

Data Availability Statement

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.

Author Contributions

TI collected patient information and was responsible for preparing the first draft. MA was responsible for preparing the first draft and reviewing it. TI and MA analysed and interpreted patient information. SY supervised the project. All authors have read and approved the final manuscript.


This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s Note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Read more  Myxedema coma precipitated by diabetic ketoacidosis after total thyroidectomy: a case report


TS, Thyroid storm; DKA, Diabetic ketoacidosis.


— Update: 04-01-2023 — cohaitungchi.com found an additional article Myxedema coma precipitated by diabetic ketoacidosis after total thyroidectomy: a case report from the website www.ncbi.nlm.nih.gov for the keyword hypothyroidism diabetic coma.

Case presentation

A 43-year-old Asian man presented to the emergency department in our institution due to generalized weakness in April 2018. One month prior to admission, his family noted that he showed poor oral intake and consistently complained of epigastric discomfort. He was diagnosed as having impaired fasting glucose and hyperlipidemia at the age of 42 on routine medical checkup. Eight months ago, he underwent total thyroidectomy with both central and sentinel lymph node dissection due to papillary thyroid carcinoma and the pathologic stage was diagnosed as T3N1bM0 on the permanent pathologic report. After that, the first radioactive iodine (RAI) therapy was conducted and an iodine [1–3] whole body scan was planned to determine whether to perform the second RAI that was on the next day of visiting the emergency room, therefore, he had to stop the thyroid medication for 3 weeks to prepare for the examination.

At the time of admission to the emergency room, he was noted to be somnolent and had a decreased level of consciousness. He opened eyes to pain, showed inappropriate verbal response and flexion withdrawal from pain, which suggested that Glasgow Coma Scale (GCS) was 10 out of 15. On physical examination, there was no pretibial edema and his pupils were equal in size and normally reactive to light. His abdomen was slightly distended with decreased bowel sound and his extremities were cold. His blood pressure was 127/96 mmHg, heart rate was 101 beats per a minute, and respiratory rate was 25 breaths per a minute with oxygen saturation 97% on room air. He was in a hypothermic state and his tympanic temperature was approximately 34.0 °C. Chest radiography revealed the findings of gastroparesis and paralytic ileus as presented in Fig. ​Fig.1.1. An electrocardiogram at presentation showed sinus tachycardia with QT prolongation by 537 ms of corrected QT interval (Fig. ​(Fig.22).

Arterial blood gas analysis revealed a state of metabolic acidosis: a pH of 7.00, partial pressure of carbon dioxide in arterial blood (PaCO2) of less than 10 mmHg, bicarbonate (HCO3) of less than 10 mmol/L, and base excess of − 34.6. Laboratory findings suggested hyperglycemia with glycosuria and ketoacidosis, which are presented in Table 1. Considering the history of total thyroidectomy and planned schedule for RAI, a thyroid function test (TFT) was conducted and revealed severe hypothyroidism. He was found to have a thyroid-stimulating hormone (TSH) of 34.126 uIU/mL (0.55–4.78 uIU/mL) and free thyroxine (T4) of less than 0.01 ng/dL (0.82–1.76 ng/dL) and triiodothyronine (T3) of less than 0.01 ng/mL (0.6–1.81 ng/mL). Even though he did not have any history of diabetes mellitus, we checked his glycated hemoglobin (HbA1c) due to hyperglycemia. Finally, the value of HbA1c was 16.5% which met the criteria for a diagnosis of diabetes.

He was admitted to the intensive care unit (ICU) for the management of DKA and myxedema coma. He received intravenously administered fluid with electrolytes and an immediately applied insulin pump. For hormonal replacement, liothyronine 5 mcg two times per day and levothyroxine 175 mcg once daily were administered via a nasogastric tube. He instantly responded to the therapy with a favorable clinical improvement. His mental status started to improve several hours after treatment and at the third day of hospitalization he showed a GCS of 15/15; his body temperature increased from 34 °C to 36.5 °C approximately 10 hours after admission. The metabolic acidosis was corrected 6 hours after administration of intravenously administered fluid with insulin pump and hyperglycemia was also improved; the insulin pump was discontinued then and switched to subcutaneous insulin 1 day after hospitalization. Repeated TFT before discharge revealed TSH of 21.798 uIU/mL (0.55–4.78 uIU/mL), free T4 of 1.02 ng/dL (0.82–1.76 ng/dL), and T3 of 1.04 ng/dL (0.6–1.81 ng/mL). The clinical course of this patient was summarized in Table 2. During the hospitalization, a workup for diabetes mellitus was performed and there was no evidence of pancreas mass or pancreatitis on abdominal computed tomography (Fig. 3). Results from investigations for diabetes mellitus showed a fasting c-peptide of 1.08 ng/mL (0.48–3.30 ng/mL), anti-islet cell antibodies (ab) negative, and glutamic acid decarboxylase (GAD) ab of 0.01 U/ml which suggested that a diagnosis of type 2 diabetes mellitus would be appropriate.

He was discharged from surgical ICU after 2 days, stayed for a further 8 days on the general ward and was discharged on the 11th hospital day with tolerable status. The dose of thyroid hormone medications was subsequently reduced at our out-patient clinic after he was discharged and an endocrinologist recommend insulin with orally administered hypoglycemic agents.


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