Hypothyroidism is a condition affecting up to 5% of the global population, is more prevalent in women, and tends to develop slowly over time. It often presents with non-specific symptoms that may overlap with those of other disorders, which can make diagnosis challenging.^[1] Common symptoms of hypothyroidism include mild to moderate weight gain, fatigue, poor concentration, depression, and menstrual irregularities, often leading to delayed or misdiagnosed treatment. These symptoms occur due to a deficiency in thyroid hormones, which play a critical role in regulating metabolism, energy production, and various physiological functions. If left untreated or undertreated, hypothyroidism can result in serious health complications, including cardiovascular disease, increased cholesterol levels, and even a heightened risk of mortality.^[2]

In some cases, long-standing, untreated hypothyroidism may lead to more uncommon and severe manifestations, one of which is Hoffmann’s syndrome. This rare form of hypothyroid myopathy presents with muscle pseudohypertrophy, especially in the lower limbs, alongside proximal muscle weakness, muscle stiffness, and painful muscle cramps. Hoffmann syndrome is most commonly seen in adults with chronic hypothyroidism and can significantly impair quality of life if not promptly diagnosed and managed.^[3] The pathophysiology of Hoffmann’s syndrome involves the effects of thyroid hormone deficiency on muscle metabolism, leading to abnormal muscle growth and functional deterioration. This case highlights the importance of recognizing Hoffmann’s syndrome as a rare but significant complication of untreated hypothyroidism, particularly in patients presenting with unexplained muscle-related symptoms.

A 29-year-old man who had no noteworthy medical history before arrived at the outpatient department complaining of swelling in his right leg and ongoing calf muscle stiffness that had been present for two weeks. The swelling gradually worsened without identifiable triggers, while the stiffness increased with walking and stair climbing but improved with rest. Over the past 4–5 years, the patient experienced gradual weight gain, and for the past 1.5 years, he reported intermittent numbness in both upper and lower limbs after prolonged inactivity. Additionally, over the past year, he noted easy fatigability along with progressive difficulty in walking and climbing stairs.

The patient also reported a history of difficulty rising from a seated position, often having to push himself up with his arms—a finding consistent with a positive Gowers' sign. He mentioned that despite this, he had not experienced any other abnormal muscle enlargement or any facial muscle weakness. In addition, he denied episodes of sustained muscle contractions, episodic quadriparesis, or significant fluctuations in muscle strength throughout the day. On general physical examination, the patient’s height was 165 cm, weight was 85 kg, and BMI was 30 kg/m ² . His heart rate was 65 beats per minute with a regular pulse, and blood pressure was 120/80 mmHg. No lymphadenopathy or neck mass was observed.

On local examination, the calf muscles of the right leg were enlarged(Fig. 1A, B) , with no irregular surface or ill-defined boundary. There was no increase in temperature or tenderness noted. Lower limb muscle circumference was greater on the right (38 cm) compared to the left (34 cm), with weakness observed in the pelvic girdle muscles. Gower’s sign was positive, and deep tendon reflexes were delayed. The remaining lower limb muscles showed normal power and tone, with no fasciculations. Examination of the central nervous system (CNS) revealed weakness in the lower limbs, along with delayed deep tendon reflexes, but otherwise no abnormal findings.

The examination of the respiratory system (chest), cardiovascular system (CVS), and abdomen did not reveal any noteworthy findings.

Baseline laboratory tests, including complete blood counts (CBC), liver function tests (LFTs), renal function tests (RFTs), and coagulation profile, were within the normal range. In the first week, laboratory results showed creatine phosphokinase (CPK) 7302 U/L (elevated, normal range: 25–195 U/L), creatine kinase-MB (CK-MB) 152 U/L (elevated, normal range: <25 U/L), thyroid-stimulating hormone (TSH) 79.5 µU/mL (elevated, normal range: 0.4–4.5 mIU/L), and T4 0.78 µg/dL (decreased, normal range: 10.3–24.7 pmol/L), indicating elevated muscle enzyme levels and thyroid dysfunction (hypothyroidism). Antinuclear antibody (ANA) and extractable nuclear antigen (ENA) profiles were negative.

A Doppler ultrasound of the lower limbs (arterial) showed no evidence of cellulitis or deep vein thrombosis (DVT). CT angiography of both lower limbs was normal, with mildly increased bulk in the right calf muscles but no inflammatory changes, masses, or subcutaneous soft tissue air.

MRI of the lower legs revealed asymmetrical hypertrophy of the posterior muscle compartment (gastrocnemius and soleus) in both calves, more pronounced on the right side (R >L), with no edema or fatty degeneration. (Fig. 2A, B) Nerve conduction studies (NCS) and electromyography (EMG) showed no electrophysiological evidence of myopathy or myositis at present. A muscle biopsy was not performed.

The patient was diagnosed with Hoffmann syndrome based on clinical features of muscle pseudohypertrophy, weakness, and stiffness, particularly in the calf muscles, along with elevated TSH and low T4 levels . The absence of primary myopathy, myositis, or vascular abnormalities further supported this diagnosis.

The patient was started on levothyroxine 150 μg once daily, along with physiotherapy. He responded well to this regimen, with significant improvement in muscle stiffness and a reduction in calf muscle size. Additionally, muscle enzyme levels declined, and thyroid function progressively normalized(Table 1) .

This case illustrated a rare presentation of hypothyroid myopathy known as Hoffman syndrome, where the patient presented with progressive calf muscle stiffness, visible pseudohypertrophy, and difficulty rising from a seated position, indicating proximal muscle weakness.

A thorough history and examination helped exclude several important differential diagnoses. There was no history of childhood-onset symptoms or progressive difficulty in walking suggestive of Duchenne or Becker muscular dystrophies. Features of facioscapulohumeral dystrophy were absent, including difficulty raising the shoulders, scapular winging, or facial muscle weakness. No signs of sustained muscle contractions were noted, ruling out myotonic dystrophy. Episodic weakness seen in hypokalemic and hyperkalemic periodic paralysis was not reported. Myasthenia gravis was considered unlikely due to the absence of fatigability or diurnal variation in strength. There were no constitutional or dermatological symptoms to support inflammatory myopathies such as polymyositis or dermatomyositis. Additionally, systemic, metabolic, and endocrine causes were excluded based on the absence of relevant clinical features: there were no signs of diabetes mellitus, Cushing syndrome, or parathyroid dysfunction.

Similar rare cases of Hoffmann’s syndrome were reported, including a 61-year-old Western European man who presented with myalgia, myxedema, and pseudo hypertrophy of the calf muscles, closely resembling our case. His laboratory findings showed significantly elevated TSH and CPK levels, mirroring our patient’s results. Additionally, muscle MRI demonstrated hypertrophy of the lower limb muscles without evidence of myositis or fatty degeneration, consistent with our imaging findings. EMG in this case showed spontaneous activity, whereas in our patient, it was normal. With thyroxine therapy, his muscle weakness gradually improved over six months, aligning with the expected treatment response.^[4]

Similarly, another reported case described an adult male with muscular cramps, myalgia, weakness, and pseudo hypertrophy, along with facial edema and voice changes. His laboratory findings included markedly elevated muscle enzymes, undetectable T4 levels, and increased TSH, reinforcing the strong link between hypothyroidism and myopathy. Electrophysiological studies in hypothyroid myopathy cases have demonstrated myopathy, neuropathy, or mixed patterns, yet our patient’s EMG findings were entirely normal. The patient in this case had autoimmune thyroiditis, and his symptoms improved significantly after three months of thyroxine therapy, underscoring the critical role of early hormone replacement.^[5]

While Hoffmann’s syndrome is generally considered a reversible myopathy, variability in muscle response has been observed. A case involving a 21-year-old male demonstrated persistent hypertrophy despite biochemical and symptomatic improvement with thyroxine therapy.‌^[6] In contrast, another patient with a six-year history of calf hypertrophy, proximal muscle weakness, and muscle cramps developed cardiac involvement, further illustrating the spectrum of disease severity. His echocardiogram revealed left ventricular systolic dysfunction, a finding absent in our case. Since our patient exhibited no cardiac symptoms or abnormalities, he was not assessed for heart failure. However, this comparison highlights the importance of early diagnosis and timely thyroid hormone replacement, as prolonged disease duration, such as the six-year hypertrophy in the latter case, may contribute to additional complications.^[7]

Our case of Hoffmann’s syndrome presented with typical features of hypothyroid myopathy, including muscle stiffness, pseudohypertrophy, and biochemical evidence of hypothyroidism. Unlike some reported cases, EMG findings were normal, and no cardiac involvement was observed. The case emphasizes the need for early recognition and management, as delayed treatment can lead to prolonged muscle hypertrophy and potential complications. Given the variability in muscle response, long-term follow-up is essential to assess whether hypertrophy fully resolves or persists despite hormone replacement therapy.

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The authors have declared that no competing interests exist.

No additional data is available for this study.