Rapid Development of Anterotibial Compartment Syndrome and Rhabdomyolysis in a Patient with Primary Hypothyroidism and Adrenal Insufficiency

Introduction

S evere myopathy with rhabdomyolysis is rarely the presenting feature of primary hypothyroidism. Such a presentation has been described in hypothyroid patients as a reaction to statin drugs or as a consequence of severe exercise, but seldom spontaneously. A combination of endocrine and electrolyte abnormalities as well as susceptibility of the anterotibial muscle compartment (ATC) may have led to his unusual presentation.

Patient

A previously well 22-year-old male university student presented to the emergency department with a one-month history of shin splints, tiredness, and cold intolerance. His feet had been swollen and tingling for 3 days. There was no history of unusual or excessive exercise or of his having taken statins or other drugs or alcohol.

On examination, he was lethargic with mild skin hyperpigmentation. His heart rate was 65 per minute and supine blood pressure was 150/110 mmHg without postural change. There was nonpitting edema of the lower legs without muscle wasting, absent ankle tendon reflexes, and 1/5 power of ankle dorsiflexion bilaterally.

His serum sodium concentration was 110 mM, potassium 6.9 mM, creatinine 410 μM, creatine kinase (CK) >25,000 IU/L (normal <220 IU/L), free thyroxine 2.5 pM (normal 12–22 pM), thyrotropin >100 mIU/L (normal 0.3–4 mIU/L), and urine myoglobin 20.1 mg/L (normal <1 mg/L).

The provisional diagnosis was of rhabdomyolysis and consequent acute renal failure with associated bilateral lower leg anterior compartment syndrome (ACS) associated with severe primary hypothyroidism. Primary adrenal insufficiency, suspected because of the presence of recent skin hyperpigmentation, was confirmed by an early-morning serum cortisol of 79 nM (normal 200–700 nM) and plasma adrenocorticotrophic hormone of 969 pM (normal 2–11 pM). Antithyroid peroxidase autoantibody titer was 1580 U (normal <60 U), and the adrenal autoantibody titer to steroid-21 hydroxylase was 8.3 U (normal <1 U).

Hyperkalemia was urgently treated with nebulized salbutamol, intravenous calcium gluconate, plus dextrose, and insulin infusion as well as oral calcium resonium. Normal saline was infused to counter any prerenal failure and the severe hyponatremia. With these measures, there was clinical and biochemical improvement after 3 hours to serum sodium of 116 mM, potassium 4.7 mM, creatinine 330 mM, and narrowing of the QRS complex on the electrocardiogram from 145 to 110 milliseconds.

He was treated with hydrocortisone 100 mg every eight hours, and the dosage was tapered from the third day to 30 mg daily after 1 week, fludrocortisone 100 μg daily, and thyroxine 500 μg as a stat dose orally, and then 200 μg daily. He steadily improved and renal failure resolved within one week. Serum CK remained elevated at >25,000 IU/L on discharge 1 week after admission and was still mildly elevated at 840 IU/L 4 weeks later when thyroid function was normal.

Magnetic resonance imaging (MRI) of his legs at presentation showed changes consistent with swelling, inflammation, and necrosis confined to anterior tibial muscles typical of ACS, with sparing of posterior calf muscles (Figs. 1 and 2). Over the ensuing 8 weeks, dorsiflexion did not improve, nerve conduction studies confirmed bilateral common peroneal nerve paralysis, and repeat MRI was unchanged. Bilateral tibialis posterior to tibialis anterior tendon transfers were later performed to enable him to walk without ankle-foot orthoses.

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FIG. 1.

Lower leg magnetic resonance imaging axial T1 with anterior compartment muscles showing altered signal swelling and loss of normal muscle striations.

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FIG. 2.

The sagittal view of right lower leg with fat saturation emphasizes the difference between the two compartments.

Discussion

This young man had an unusual combination of severe autoimmune primary hypothyroidism, adrenal insufficiency, myopathy, hyponatremia, and hyperkalemia leading to ACS, rhabdomyolysis, and reversible acute renal failure. A loading dose of oral thyroxine was chosen for the acute management of myxedema coma and in view of the lack of availability to us of parenteral triiodothyronine that might otherwise have provided faster reversal of hypothyroidism. The severity of his bilateral ACS caused irreversible pressure damage to both common peroneal nerves despite his short history, prompt diagnosis, and treatment. Because his was a chronic ACS, present >48 hours in contrast to acute trauma, urgent decompressive fasciotomy was not performed.

Rhabdomyolysis has been reported in adrenal insufficiency and in combined autoimmune primary adrenal and thyroid failure or Schmidt's syndrome, as here (1,2). More commonly, even in severe hypothyroidism, there are only minor symptoms of hypothyroid myopathy such as stiffness, aching, and modest CK elevation (3). Muscles may be enlarged and pale when examined, because of interstitial edema and mucinous deposits, but frank muscle necrosis with rhabdomyolysis is rare, perhaps requiring an anatomic predilection related to the anterotibial compartment.

ACS in a patient with hypothyroidism was first reported in 1993 (4) and a second case 2 years later (5). ATC surgical release was performed in each case, but without benefit (4,5). In our patient, the interstitial myositis, myopathy, and perhaps the physical structure of his anterior compartment may have combined to cause local muscle necrosis without symptoms or signs of myopathy elsewhere, as demonstrated by the normal clinical findings and MRI appearance in muscle groups outside the ATC. We speculate therefore that there may be an anatomic susceptibility to ACS in selected patients with severe primary hypothyroidism. In contrast to the reversibility of acute traumatic ACS, the spontaneous development of the syndrome over several days to weeks, associated with complete foot drop and severe muscle necrosis on MRI, argues against the utility of decompression as an aid to peroneal nerve recovery. In a related context, it has been suggested that postexertional MRI may have a useful screening role in the investigation of chronic compartment syndrome that usually presents with recurrent episodes of pain on exercise (6). Future investigation by MRI of the lower legs in hypothyroid patients with myopathy and raised serum CK without rhabdomyolysis may show evidence of differential anatomic muscle appearances short of frank necrosis.