Thyroid storm: a case of haemodynamic failure promptly reversed by aggressive medical therapy with antithyroid agents and steroid pulse

Abstract

Hyperthyroidism is a common metabolic disorder, although its presentation as an endocrine emergency called thyroid storm is rare. Here we review a case of a thyroid storm as the initial presentation of thyrotoxicosis, with multiple organ failure and haemodynamic collapse due to low-output cardiac dysfunction. Quick intervention with aggressive antithyroid therapy, including steroid pulse, and supportive intensive care measures led to an outstanding improvement and full recovery. The present case clearly shows the beneficial impact of initial clinical suspicion resulting in an early diagnosis and intensive therapy. Moreover, it supports the additional role of steroids to aggressive antithyroid strategy in order to control associated deleterious systemic inflammatory reactions.

Background

Thyroid storm is a rare life-threatening condition characterised by severe multisystem involvement and exaggerated clinical manifestations of thyrotoxicosis. Although thyroid storm can develop in patients with long-standing untreated hyperthyroidism (Graves’ disease, toxic multinodular goitre or solitary toxic adenoma), it is often precipitated by an event such as thyroid or non-thyroidal surgery, trauma, infection, acute iodine load or parturition.^1–3 The incidence of this disorder has been estimated at 0.22% of all patients with thyrotoxicosis and described at 0.20 per 100 000 per year in a national survey from Japan.^{1 4} Presentation as haemodynamic collapse with multiorgan dysfunction is uncommon.⁴ Without treatment, mortality ranges from 80% to 100%, whereas with the recommended therapy it reaches 50% of all cases, and the most common cause of mortality is multiple organ failure.^5–7 The exact mechanisms remain unclear, but it is known that untreated hyperthyroidism and acute events can trigger the development of this condition.^1–3

The clinical features of a thyroid storm are typically an exaggeration of cardiovascular, neurological, gastroenterological and physical signs and symptoms of hyperthyroidism, accompanied by signs of multiorgan decompensation.1–3 6 7 From the cardiovascular standpoint, this hypermetabolic state and its tremendous oxygen demand normally manifest with increased resting heart rate, cardiac contractility and cardiac output.^{4 5 8} Nevertheless, recent reports suggest that besides the direct toxicity of thyroid hormones, there is an inflammatory state generated by pathological thyroid autoimmune mechanisms that may play a major role in cardiac and extracardiac dysfunction.^8–10 To reverse this chain of organ failure, in addition to aggressive antithyroid therapy, glucocorticoid therapy administered as an intravenous pulse is gaining importance. Besides reducing T4-to-T3 conversion, it may act directly on the underlying autoimmune process, if thyroid storm is due to Graves’ disease, and treat potentially associated limited adrenal reserve.^{8 11 12}

We describe an unusual case of a thyroid storm in a man without a previous diagnosis of hyperthyroidism. The patient presented with low-output cardiac failure that evolved into cardiogenic shock conducting to multiorgan dysfunction. This life-threatening condition was successfully reversed with aggressive medical therapy based on antithyroid drugs and glucocorticoids.

Case presentation

A 52-year-old Caucasian man, without significant medical history and taking no regular medications, was admitted to the emergency department in May 2017, with general malaise, fatigue, palpitations, peripheral oedema and diarrhoea for 4 days. He had lost 15% of his body weight in 3 months. The patient was normothermic (37.2°C), anxious, with hand tremor and cold extremities, tachycardic with an irregular pulse rate of 131 beats/min, normotensive (blood pressure: 123/76 mm Hg), polypnoeic (22 respiratory cycles/min) with a peripheral oxygen saturation of 97% on room air, icteric with severe bilateral exophthalmos (figure 1), and thyroid gland enlargement (figure 2), irregular heart sounds, bibasal rales and major lower limb oedema.

Figure 1.

Bilateral exophthalmos.

Figure 2.

Thyroid enlargement.

ECG confirmed atrial fibrillation. Chest X-ray showed cardiomegaly with a cardiothoracic index of 0.6. The preliminary serum laboratory tests showed mild renal failure: creatinine 1.3 mg/dL (114.9 μmol/L) and urea 99 mg/dL (16.5 mmol/L); serum electrolytes: hyponatraemia 129 mmol/L and hyperkalaemia 6.3 mmol/L; mild hepatic failure: aspartate aminotransferase 215 U/L, alanine aminotransferase 334 U/L, alkaline phosphatase 190 U/L, γ-glutamyl transferase 73 U/L, albumin 2.5 g/dL, total bilirubin 4.09 mg/dL, total cholesterol 104 mg/dL, partial thromboplastin time 37 s (normal: 25.4–34.3 s), prothrombin time 30.2 s (normal: 12.8–15.7 s), international normalised ratio 2.02 and glucose 87 mg/dL; complete blood counts were within the normal range, with platelets near the lower limit of 155×10⁹/L; markers of cardiac dysfunction: N-terminal pro B-type natriuretic peptide 12 620 pg/mL (positive >900), creatine kinase 220 U/L (normal: 38–175 U/L), creatine kinase-muscle/brain 51 U/L (normal: 0–24 U/L) and troponin I 0.07 ng/mL (normal: <0.04 ng/mL); thyroid function tests: thyroid-stimulating hormone (TSH) <0.005 μU/mL (normal: 0.38–5.33 μU/mL), free triiodothyronine (FT3) 5.3 pg/mL (normal: 2.5–3.9 pg/mL), free thyroxine (FT4) 3.1 ng/dL (normal: 0.6–1.1 ng/dL) and autoantibodies to the thyrotropin receptor (TRAb) 8.5 UI/L (normal: ≤1.6 UI/L). With these results a diagnosis of severe hyperthyroidism was made. The patient was started promptly on treatment with propranolol 40 mg every 8 hours and methimazole 30 mg every 8 hours. In less than 6 hours a rapid deterioration of his status was observed with hypotension (blood pressure: 89/45 mm Hg), tachyarrhythmia (heart rate: 137 beats/min) and signs of poor peripheral perfusion. Arterial gases on 35% by nasal cannula showed pH of 7.38, partial pressure of oxygen 160 mm Hg, partial pressure of carbon dioxide 16 mm Hg, HCO₃⁻9.5 mmol/L, base excess −15.6 mmol/L (normal: −2.0–3.0), K⁺ 6.5 mmol/L and lactate 8.4 mmol/L.

The diagnosis was thyroid storm with multiorgan involvement, predominantly cardiovascular with signs of circulatory shock. The patient was transferred to the intensive care unit for further evaluation and management. Headboard echocardiography indicated a biauricular and left ventricular (LV) dilatation with global reduction in contractility, severely reduced left ventricular ejection fraction (LVEF) of 19% and a distended inferior vena cava (IVC) without inspiratory collapse.

The patient’s condition deteriorated dramatically with profound lethargy, dyspnoea, hypotension, diaphoresis and capillary refill time of 3 s. There was evidence of cardiac instability with atrial fibrillation and a heart rate oscillation between 30 and 130 beats/min, culminating in extreme bradycardia with haemodynamic collapse and respiratory arrest. Advanced support measures were promptly initiated with 1 mg atropine followed by vasomotor and inotropic infusions and orotracheal intubation for mechanical ventilation. At this critical point, norepinephrine and dobutamine doses reached a maximum value of 70 µg/min and 8 µg/min, respectively. Aggressive medical management of the thyroid storm was initiated with 1 g intravenous methylprednisolone bolus, followed by hydrocortisone 100 mg every 8 hours, propylthiouracil 200 mg every 4 hours, Lugol’s solution 10 drops every 8 hours and cholestyramine 4 g every 6 hours.

After haemodynamic stabilisation, the patient developed hyperthermia (39.8°C) refractory to pharmacological measures, and thermal blanket was successfully applied to maintain a temperature of 36°C. As listed in table 1, the patient exhibited renal and haematological worsening during his first days in the intensive care unit. While the patient recovered from this circulatory collapse, the doses of vasopressors and inotropes were progressively reduced.

Table 1.

Laboratory findings during and after hospitalisation

	1	2	3	4	5	6	7	8	9	10	11	14	26	28	32	71
Parameter (reference range and units)
Haemoglobin (13–17 g/L)	138	156	153	146	156	174	148	163		151	152	146	134	132	135	141
Leucocytes (4.0–10.0×109/L)	6.34	9.84	7.55	6.51	7.83	8.77	12.05	13.76		10.59	14.58	10.17	5.32	5.77	4.84	9.28
Platelets (150–400×109/L)	155	141	136	99	95	100	94	78		169	218	271	297	180	225	283
PTT (25.4–34.3 s)	40.7	39.5	37.2	31.7	29.4	27.9	30.7	35.8
PT (12.8–15.7 s)	30.6	38.2	29.9	24.2	20.7	18.9	16.4	19.7
Creatinine (0.7–1.2 mg/dL)	1.3	1.6	1.7	1.3	0.6	0.7	0.5	0.5		0.5	0.6	0.5	0.6	0.3	0.6	0.6
Urea (11–50 mg/dL)	104	147	187	212	131	95	66	82		52	49	57	27	26	22	37
AST (15–41 U/L)	215	1356	488	230	104	80	60	58		60	71	58	40	23	38	51
ALT (14–54 U/L)	334	835	645	457	265	192	120	139		107	115	103	66	39	48	54
FA (38–126 U/L)	190	140	122	122	114	151	114	127		122	109	104	146			117
γ-GGT (7–64 U/L)	73	57	54	48	59	188	170	142		248	132	151	158			49
Total bilirubin (0.3–1.2 mg/dL)	4.3	5.14	4.25	3.07	3.95	4.74	3.72	5.7					1.09			1
LDH (≤248 IU/L)	244	1041	338	197	162	190	186	162		191	221	180	191		160	191
TSH (0.38–5.33 μUI/mL)		<0.005	<0.005			0.032				<0.005			0.006		0.009	0.014
FT4 (0.6–1.1 ng/dL)		3.1	2.3			1.8				0.3			0.4		0.3	0.8
FT3 (2.5–3.9 pg/mL)		5.3	2.8			2.4				1.7			1.8		1.7	1.6
TRAb (≤1.6 UI/L)		8.5
pH arterial (7.35–7.45)	7.38	7.46	7.48	7.45	7.47	7.43	7.52	7.52	7.51		7.52	7.53
HCO3 − arterial (21–28 mmol/L)	9.5	29.9	32	30.6	33.5	28	37.6	35.1	35.1		31	26.7
BE (−2–3 mmol/L)	−15.6	6.1	8.5	6.6	9.8	8.2	34.8	12.2	12.1		8.1	4
Lactate (0–1.3 mmol/L)	8.4	2.3	2.4	1.8	1.7	1.8	1	1.1	1.3		1.9	2.1

ALT, alanine aminotransferase; AST, aspartate aminotransferase; BE, base excess; FA, alkaline phosphatase; FT3, free triiodothyronine; FT4, free thyroxine; γ-GGT, γ-glutamyl transferase; LDH, lactic dehydrogenase; PT, prothrombin time; PTT, partial thromboplastin time; TRAb, thyrotropin receptor autoantibodies; TSH, thyroid-stimulating hormone.

On day 4 after admission, the patient showed a marked improvement in his neurological status, being conscious and responding to simple orders. He remained haemodynamically stable without further need for adrenergic support, and he was extubated the day after. Given the clinical, haemodynamic and ventilatory stability, on day 6 after admission the patient was transferred to the internal medicine department to continue his recovery and further treatment. Thyroid ultrasound confirmed that our 167 cm tall patient had a diffuse multinodular goitre, with the right and left lobes measuring 61×25×20 mm and 61×20×18 mm, respectively, showing higher dimensions when compared with the age-adjusted and size-adjusted normal range of 40−50×13–18×13–18.^13–15 Repeat cardiac echo on day 23 after admission revealed a marked reduction of biauricular dilatation with normalisation of LV dimensions, recovery of global contractility and LV systolic function with an ejection fraction of 63%. Non-dilated IVC with adequate respiratory kinetics was also observed.

The patient had an uneventful stay in the internal medicine department and he was discharged on the 29th day of hospitalisation with advice for treatment with thiamazole 15 mg every 8 hours and regular follow-up.

Outcome and follow-up

After hospital discharge, the patient returned to his daily life with no evidence of brain or cardiac injury, significant myopathy or other objective organ dysfunction.

Discussion

The diagnosis of thyroid storm is primarily clinical, based on the presence of systemic decompensation in a patient with severe thyrotoxicosis.1 2 4 5 7 16 Despite its limitations, to better evaluate thyrotoxic crisis, Burch and Wartofsky proposed a score system based on clinical criteria where a score ≥45 is highly suggestive of this diagnosis.1 2 7 16 Our patient had a strongly suggestive score of 65, corroborated by biochemical evidence of hyperthyroidism, with marked suppression of TSH and highly elevated FT3 and FT4.

The case we describe had some strong and unusual points. First, there was no history of thyroid dysfunction; therefore, an initial presentation of hyperthyroidism as a thyroid storm was unexpected. However, our patient comes from a disadvantaged socioeconomic context, deprived of a primary healthcare network, where this endocrinopathy could have been diagnosed and managed in a timely manner.

Second, although hyperthyroid crisis typically is a hyperdynamic state with a high cardiac output, our patient presented a rare low-output cardiac failure, perhaps triggered by the contractile dysfunction related to thyrotoxic cardiomyopathy, relative adrenal insufficiency and bradycardia secondary to electrical instability probably exacerbated by propranolol.1 4 5 8 Third, although aggressive antithyroid therapy is known to correct the cardiotoxic injury leading to recovery of myocardial contractility and LVEF, our option was to also use pulsed steroids in an attempt to eliminate the inflammatory state that may contribute to further myocardial derangement. The 2016 American Thyroid Association Guidelines for management of thyroid storm support that glucocorticoids reduce T4-to-T3 conversion, promote vasomotor stability and possibly treat an associated relative adrenal insufficiency.¹² There is an increasing evidence that thyrotoxic cardiomyopathy results from the direct effect of high thyroid hormone levels and from other factors such as autoimmune inflammatory reactions.^{8 9} This inflammatory involvement may be extracardiac, resulting in liver dysfunction also seen in our patient.⁸ Fourth, a previous description stated a clear discrepancy between reduction in thyroid hormone levels and improvement of cardiac function in a patient also treated with a steroid pulse.⁸ In our case, despite the progressive normalisation of thyroid hormone levels in the first 10 days of treatment, the surprising recovery of our patient’s condition in 4 days seems to support a potential advantageous intervention in the inflammatory state by the steroid pulse. Fifth, it is described that even in critical cases in which mortality is avoided, significant morbidity is more likely to occur.² Supporting our approach, this patient had an amazing recovery without evident cerebral injury, diffuse atrophic myopathy, and renal, cardiac or liver function impairment. Sixth, our patient has a full clinical picture of Graves’ disease with documented multinodular goitre, but unlike the few previously reported cases of thyroid storm with low-output heart failure, he had only a modest rise of TRAb levels to 8.5 UI/L.

This case is complex but strongly demonstrates that in worst scenarios of this life-threatening condition, steroid pulse may be a valid and effective therapeutic option.

Learning points.

• The non-specific presentation of thyroid storm which often overlapped with other severe illnesses can make the diagnosis and treatment a major challenge.

• Prompt recognition and intensive care management of this endocrine emergency, which harbours high morbidity and mortality, is critical to improve patient outcome.

• Our case is an opportunity to highlight the occurrence of a rare low cardiac output thyroid storm.

• Furthermore, clinical features with poor outcomes, such as altered mentation and serum bilirubin level >3 mg/dL, may be a trigger point to identify patients who may benefit most from an aggressive therapeutic strategy.

• Latest case reports indicate that steroid pulse has a potential major role in treating the relative adrenal insufficiency and controlling the systemic inflammatory state associated with this rare endocrine emergency.

• The patient’s rapid cardiovascular improvement gives strength to this approach as a key therapeutic option in a thyroid storm, reducing hospitalisation time in intensive care units and enhancing global outcomes.