Recurrent thyroid storm induced by heretofore unrecognised causes in a patient with thyroid cancer

Abstract

An unusual encounter of a thyroid storm, on two separate occasions, is reported in a patient with metastatic differentiated thyroid cancer following initially direct trauma to, and later tumour embolisation of, a metastatic skeletal lesion. Shortly after a fall, our patient presented with pain and swelling in the right shoulder, high fever, change in mental status, anorexia, nausea and vomiting, tachycardia and dehydration. The laboratory tests were consistent with hyperthyroidism. As the patient improved, arterial embolisation of the large right humerus metastasis was performed to decrease the tumour burden. The patient, however, developed a similar clinical and biochemical picture to that at her presentation, with a very high free thyroxine (T₄) level, a few days after successful embolisation. Treatment of the thyroid storm was initiated and the patient eventually improved. Awareness of such occurrences is helpful in early diagnosis and effective management of this potentially fatal complication.

BACKGROUND

Differentiated thyroid cancer is the most common endocrine malignancy, with an overall excellent prognosis.^1,2 The presence of distant metastasis especially in the bone would dramatically worsen the prognosis.³ Nevertheless, patients with differentiated thyroid cancer and distant metastasis, including those with bone lesions, may survive for many years.^4–6

Functional metastasis of thyroid cancer, especially differentiated follicular thyroid cancer, had been reported with lung, bone and even liver metastasis.^7–10 Rarely in such cases, clinical thyrotoxicosis occurred spontaneously,^7,10,11 or more commonly after treatment with radioactive iodine.^9,12 Thyroid storm and death have also only rarely been reported to occur, mostly after radioactive iodine treatment, in patients with large functional metastasis of differentiated thyroid cancer.^9,12,13

Our patient presented initially with a thyroid storm secondary to necrosis of the tumour caused by trauma, with spontaneous slow improvement. She later developed a similar clinical picture upon arterial embolisation of the metastatic tumour. A recurrent thyroid storm from divergent aetiologies in a given patient with metastatic thyroid cancer has not, to our knowledge, been reported before.

CASE PRESENTATION

Presentation after trauma

The patient was a 74-year-old female with a metastatic follicular variant of papillary thyroid cancer. She had total thyroidectomy with neck dissection 15 years earlier. She was known to have bone metastasis to the right humerus complicated by a fracture requiring internal fixation and nailing shortly after her initial presentation. She received radioactive iodine treatment on five occasions, with an accumulative ¹³¹I dosage of 993 mCi. She had palliative radiotherapy to the right humerus twice, for a total of 1800 cGy because of local pain. She was on levo-thyroxine 112 μg once daily.

The patient was in her usual state of health until 2 months prior to her presentation, when she had a fall onto her right shoulder. She then started to have progressive swelling, heat and redness over the right shoulder, in addition to severe pain limiting movement of her upper limb. There was also history of fever, chills and confusion. She was admitted to a local hospital where she was given antibiotics intravenously for possible local infection, but with no response. She had nausea and vomiting and a decreased oral intake. She was therefore referred to our centre.

At her presentation to our hospital, she was noted to be tachycardic, with a pulse of 110; her blood pressure was 126/62 mm Hg. She had fever up to 38°C. She was found to have swelling, redness and tenderness over the right shoulder. The swelling was diffuse reaching to the elbow joint and up to the neck superiorly without fluctuation. She had severe restriction of her right shoulder movements.

The initial laboratory investigations after admission revealed white blood cell count 19.6×10⁹/l (3.8–9.8) with 80% as neutrophils, haemoglobin 92 g/l (120–150) and platelets 371×10⁹/l (140–440); prothrombin time, activated partial thromboplastin time and creatinine were normal. The patient’s thyroglobulin level was >5000 μg/l (<2), thyroid-stimulating hormone (TSH) was <0.02 mIU/l (0.4–3.5) and free thyroxine (T₄) was 32 pmol/l (10–22). Albumin was 30 g/l (36–50).

The patient was admitted, levo-thyroxine was withheld throughout her admission. Investigation to rule out infectious causes such as abscess formation or osteomyelitis was negative. x Rays of the right shoulder are shown in fig 1.

Figure 1.

(A) x Ray of the right arm shows disappearance of the proximal humerus due to tumour metastasis. The intramedullary rod and cement can be seen. (B) MRI of the same arm indicates the metastasis to the right shoulder (arrow).

The patient remained febrile with chills for more than 1 week after initiating antibiotics. She was therefore started on a non-steroidal anti-inflammatory drug (NSAID) and, shortly after, it was noted that the swelling, redness and pain improved. Her fever also subsided.

An ultrasound-guided biopsy of the shoulder mass confirmed a well-differentiated follicular variant of papillary thyroid cancer and ruled out anaplastic transformation (fig 2).

Figure 2.

Ultrasound-guided biopsy of the metastatic tumour in the right arm reveals a well-differentiated follicular pattern of the thyroid cancer metastasis.

Clinical events after arterial embolisation

As the patient improved clinically, an arterial embolisation of the tumour was planned to decrease the tumour burden and to prevent similar events in the future (fig 3).

Figure 3.

Subtracted angiography images taken (A) just before embolisation, (B) during embolisation and (C) postembolisation of the vessels supplying the metastatic mass. There was a significant decrease in arterial blood flow.

On the second day after embolisation, the patient became unwell again, with nausea, frequent vomiting, spiking fever and lethargy. She was tachycardic and her blood pressure was mildly elevated to 150 mm Hg systolic. She was transferred to the Intensive Care Unit (ICU). Laboratory tests were done (see below). A diagnosis of thyroid storm was made.

INVESTIGATIONS

Laboratory investigations after arterial embolisation

Free T₄ increased to 72 pmol/l (10–22) and total triiodothyronine (T₃) to 4 nmol/l (0.9–2.7) with suppressed TSH. Leucocyte count increased to 41×10⁹/l (3.8–9.8).

TREATMENT

The patient was treated in the ICU and later on with propylthiouracil (PTU) 200 mg rectally every 6 h, intravenous esmolol, 100 mg of hydrocortisone intravenously every 8 h and supersaturated potassium iodide (SSKI) 5 drops every 6 h. The patient’s pulse improved, vomiting stopped and thyroid hormone levels improved slowly.

OUTCOME AND FOLLOW-UP

The patient eventually improved and was discharged off l-thyroxine, as her free T₄ was still elevated, with a plan to resume it once she has become euthyroid.

DISCUSSION

The case illustrated the development of a thyroid storm (lethargy, confusion, fever, tachycardia, nausea and vomiting, in association with increased blood thyroid hormone levels) in this elderly patient on two occasions. The first was on presentation to her local hospital a few weeks after her fall, and the second was shortly after arterial embolisation of her metastatic tumour.

The diagnosis on the first presentation was made retrospectively, as the patient was transferred to our hospital while her blood T₄ level was improving and the possibility of an infectious process, especially osteomyelitis, was entertained but ruled out by multiple imaging, aspiration with negative culture and negative blood cultures. Anaplastic transformation of the metastatic thyroid tumour was also considered. This possibility was ruled out by the ultrasound-guided biopsy that showed a still well-differentiated follicular variant of papillary thyroid cancer.

The patient’s local symptoms and fever showed improvement after the use of an NSAID, which is consistent with tumour necrosis as the aetiology of her local symptoms.

The recurrence of lethargy, nausea, vomiting, high fever, anorexia and local symptoms of swelling and pain of an even more severe degree after the embolisation of the tumour, and the associated increase in thyroid hormone levels and white blood cells, did finally alert us to and confirm the diagnosis of thyroid storm secondary to necrosis of the tumour.

Cases of severe thyrotoxicosis and even of thyroid crisis have been reported to follow radioactive iodine treatment of widely metastatic follicular thyroid cancer. Fatal thyroid storms were also reported in rare cases of lung and bone metastasis after treatment with radioactive iodine.^9,12

In our patient, the trigger for tumour necrosis initially was simple trauma secondary to a fall, as the tumour was covering a large area of the arm and shoulder.

Destruction of the thyroid gland itself by trauma after an accident,¹⁴ due to metastasis to the thyroid gland from another primary tumour¹⁵ or due to destructive anaplastic thyroid cancer¹⁶ was reported to result in thyrotoxicosis.

In one report, a thyroid storm also resulted from a functioning metastatic thyroid carcinoma in a burn patient, presumably due to tissue necrosis.¹⁷ Direct trauma to metastatic functional thyroid tissues, had not, however—to our knowledge—been reported before to cause thyrotoxicosis or thyroid storm.

On the second occasion, arterial embolisation of the tumour was the cause of further tumour necrosis, thyrotoxicosis and storm. Arterial embolisation is being used infrequently to treat metastatic thyroid cancer lesions, mostly vascular bone metastases that are not amenable to surgery. It can decrease the tumour burden and improve symptoms.¹⁸ An effective embolisation of a large tumour mass could lead to necrosis of the tumour cells and the release of thyroid hormones from well-differentiated thyroid cancer cells. In one case report, iodine-containing contrast was blamed for inducing a thyroid crisis after an angiogram of a metastatic thyroid mass—due to iodine-induced hyperthyroidism.¹⁹ The mechanism of thyroid storm in our patient is most probably related to tissue necrosis, as judged by the rapid rise of the T₄ level after embolisation. This is the first report, to our knowledge, of arterial embolisation leading to thyroid storm in a patient with metastatic thyroid cancer.

LEARNING POINTS

• Direct trauma or arterial embolisation of large functional thyroid cancer metastasis can lead to severe thyrotoxicosis and thyroid crisis secondary to vast tumour necrosis.

• Awareness of such an occurrence could lead to early diagnosis and effective management of this potentially fatal complication.

• The use of β-blockers in our patient prior to arterial embolisation could have decreased the severity of the symptoms caused by the sudden release of thyroxine after embolisation.

Table 1.

Thyroid laboratory values: thyroglobulin, free thyroxine, thyroid-stimulating hormone (TSH) and total triiodothyronine (T₃) of the patient at presentation and before and after the arterial embolisation

Event	Days after admission	Thyroglobulin (<2)	Free throxine (10–22)	TSH (0.4–3.5)	T3 (0.9–2.6)
LT4 stopped	Day 1	>5000.0 μg/l	32.0 pmol/l	<0.02 mU/l	3.8 nmol/l
Arterial embolisation procedure	Day 4		24.9 pmol/l	<0.02 mU/l	2.6 nmol/l
	Day 7		29.6 pmol/l
	Day 11		27.7 pmol/l
	Day 18		17.7 pmol/l	<0.02 mU/l	2.4 nmol/l
ICU transfer	Day 19		33.5 pmol/l
	Day 20		59.0 pmol/l		3.6 nmol/l
	Day 21		65.9 pmol/l		4.0 nmol/l
	Day 23		70.6 pmol/l
	Day 24		46.9 pmol/l		2.1 nmol/l
	Day 25		45.2 pmol/l		2.5 nmol/l
	Day 26		40.1 pmol/l		1.8 nmol/l

Normal values are given in parentheses.

ICU, Intensive Care Unit; LT4, levo-thyroxine.