QJM: An International Journal of Medicine, 2023, 239–240
https://doi.org/10.1093/qjmed/hcac231
CASE REPORT
Hoffman myopathy and hypothyroidism
1
, A. Mukherjee1 and S. Malakar2
A.K. Datta
From the 1Department of Neurology, Bangur Institute of Neuroscience, IPGMER, SSKM, Sambhu Nath Pandit
Street, Bhowanipore, Kolkata 700020, West Bengal, India and 2Department of Radiology, Apollo Gleneagles
Hospital, Kolkata, West Bengal, India
Address correspondence to Dr A.K. Datta, Department of Neurology, Bangur Institute of Neuroscience, IPGMER, SSKM, 52/1A Sambhu Nath Pandit Street,
Bhowanipore, Kolkata 700020, West Bengal, India. email: amlankd@gmail.com
Learning points for clinicians
Hypothyroidism should be included in the differential
diagnosis of any patient with muscle weakness and
hypertrophy, since it is reversible on therapy. A strong
index of clinical suspicion, coupled with relevant labora-
tory investigations and judicious use of muscle magnetic
resonance imaging can aid in early diagnosis, without
the need for biopsy.
CASE
A 19-year-old male, born out of non-consanguineous mar-
riage, presented with a 6-month history of progressive proximal
predominant weakness of all four limbs, associated with muscle
aches and cramps, and prominent enlargement of both calf and
thigh muscles. He also had a hoarse voice, short stature and
generalized slowness of activities. Examination revealed a lower
motor neuron type of quadriparesis, with diminished deep ten-
don reflexes and normal cranial nerve and sensory examin-
ation. Autonomic functions were spared. Serum creatinine
kinase was raised beyond 10 times the normal limit. Thyroid
stimulating hormone level was very high (>100 IU/l), with low
free T3 and free T4 levels. Anti-thyroid peroxidase antibody was
strongly positive. Electrocardiogram revealed a low-voltage
tracing and echocardiography was remarkable for the presence
of a chink of pericardial effusion. Electromyography confirmed
a myopathic pattern of weakness.
Magnetic resonance imaging (MRI) of both thighs and calves
was done using a 3 T SIEMENS scanner, with the following
sequences: Axial: T2 turbo spin echo (TSE), coronal: T1 TSE,
short tau inversion recovery (STIR), T2 TSE, sagittal: STIR, pro-
ton density and T2 TSE. There was diffuse, symmetrical
Received: 27 September 2022
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Case report
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edematous swelling of bilateral gastrocnemius-soleus
(Figure 1A), adductors and hamstring muscles (Figure 1B), with-
out any collection or mass lesion, and preserved intermuscular
fat planes and intact neurovascular bundles. Levothyroxine re-
placement therapy was started at a dose of 1.6 mg/kg body
weight, resulting in significant improvement in muscle power
and reduced muscle bulk over next 6 months.
DISCUSSION
Hoffman myopathy (HM) is a unique form of metabolic myop-
athy noted in uncontrolled hypothyroidism, characterized by
muscle weakness, hypertrophy and stiffness.1–3 Although various
forms of muscle abnormalities are common in hypothyroidism,2
HM is extremely rare and presents with proximal weakness,
enlarged muscles, cramps and slowness of movements and
delayed deep tendon jerks, most of which were present in our pa-
tient.3 Muscle abnormalities are attributable to perturbed oxidative
and glycogenolytic metabolism, altered expression of muscle con-
tractile proteins, accumulation of glycosaminoglycans and replace-
ment of fast twitch type II fibers by slow twitch type I fibers.1,4
Gastrocnemius is the most involved muscle,1 and this was evident
in our case as well. Muscle MRI is a valuable, tool in the evaluation
of skeletal muscle disorders, based on its ability to delineate the
distribution and architecture of myopathy.5 The main differentials
considered in our case were inflammatory myositis, subacute de-
nervation myopathy, and infectious or granulomatous myopathy.
Inflammatory myopathy presents with proximal, symmetric pat-
tern of involvement, however, in our case, the affection was pre-
dominantly below the knee. Intact neurovascular bundles and
absence of focal, nodular pattern on MRI were enough to rule out
subacute denervation and infectious/granulomatous causes, re-
spectively. Although clinically, the term ‘pseudohypertrophy’ is
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Figure 1. Upper panel (A), (Left) shows increased bulk of medial compartment of both thighs. (Middle and right) MRI T2 sagittal and axial sequences reveal symmetrical
increase in bulk of both adductors (asterisk) and hamstrings (circle). Lower panel (B) shows (left) symmetric increase in bulk of calf muscles with (middle and right)
demonstrable symmetric enlargement of both gastrocnemius (circle) and soleus (asterisk). Involved muscles were conspicuous for loss of normal fibrillary pattern and
high intramuscular signal, suggestive of edema. Intermuscular fat planes are preserved.

used to denote increase muscle bulk despite weakness,1–3 in radio-
logical perspective, ‘pseudohypertrophy’ refers to enhanced
muscle volume with increased interspersed fat deposition,6 which
was not seen in our patient.
Early detection of this potentially treatable condition by la-
boratory and non-invasive techniques, such as MRI is invalu-
able for diagnosis and to achieve a favorable outcome since
initiation of levothyroxine replacement therapy at an incipient
stage can lead to a remarkable recovery.
Funding: None declared.
Conflict of interest: None declared.
References
1. Nalini A, Govindaraju C, Kalra P, Kadukar P. Hoffmann’s syn-
drome with unusually long duration: report on clinical,
laboratory and muscle imaging findings in two cases. Ann
Indian Acad Neurol 2014; 17:217–21.
2. Vasconcellos LF, Peixoto MC, de Oliveira TN, Penque G, Leite
AC. Hoffman’s syndrome: pseudohypertrophic myopathy as
initial manifestation of hypothyroidism. Case report. Arq
Neuropsiquiatr 2003; 61:851–4.
3. Mastropasqua M, Spagna G, Baldini V, Tedesco I, Paggi A.
Hoffman’s syndrome: muscle stiffness, pseudohypertrophy
and hypothyroidism. Horm Res 2003; 59:105–8.
4. Sindoni A, Rodolico C, Pappalardo MA, Portaro S, Benvenga S.
Hypothyroid myopathy: a peculiar clinical presentation of thy-
roid failure. Review of the literature. Rev Endocr Metab Disord
2016; 17:499–519.
5. Chung J, Ahn KS, Kang CH, Hong SJ, Kim BH. Hoffmann’s dis-
ease: MR imaging of hypothyroid myopathy. Skeletal Radiol
2015; 44:1701–4.
6. Lovitt S, Moore SL, Marden FA. The use of MRI in the evaluation
of myopathy. Clin Neurophysiol 2006; 117:486–95.