Hoffmann syndrome
{{Short description|Medical condition}}
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Hoffmann syndrome is a rare form of hypothyroid myopathy and is not to be confused with Werdnig-Hoffmann disease (a type of spinal muscular atrophy).
It was first documented in 1897 by Johann Hoffmann.{{Cite web |title=Myopathies associated with thyroid disease |url=https://www.medlink.com/articles/myopathies-associated-with-thyroid-disease |access-date=2023-05-28 |website=MedLink Neurology |language=en}} It has adult-onset symptoms and is comparable to the childhood-onset Kocher–Debré–Semelaigne syndrome. It is caused by low thyroid hormones (T3 and T4) with elevated TSH.{{cite journal |last1=Vignesh |first1=G |last2=Balachandran |first2=K |last3=Kamalanathan |first3=S |last4=Hamide |first4=A |title=Myoedema: A clinical pointer to hypothyroid myopathy. |journal=Indian Journal of Endocrinology and Metabolism |date=March 2013 |volume=17 |issue=2 |pages=352 |doi=10.4103/2230-8210.109672 |pmid=23776921|pmc=3683223 |doi-access=free }}{{cite journal |last1=Mangaraj |first1=S |last2=Sethy |first2=G |title=Hoffman's syndrome - A rare facet of hypothyroid myopathy. |journal=Journal of Neurosciences in Rural Practice |date=October 2014 |volume=5 |issue=4 |pages=447–8 |doi=10.4103/0976-3147.140025 |pmid=25288869|pmc=4173264 |doi-access=free }}{{cite journal |last1=Udayakumar |first1=N |last2=Rameshkumar |first2=AC |last3=Srinivasan |first3=AV |title=Hoffmann syndrome: presentation in hypothyroidism. |journal=Journal of Postgraduate Medicine |date=October 2005 |volume=51 |issue=4 |pages=332–3 |pmid=16388183}}{{cite journal |last1=Vasconcellos |first1=LF |last2=Peixoto |first2=MC |last3=de Oliveira |first3=TN |last4=Penque |first4=G |last5=Leite |first5=AC |title=Hoffman's syndrome: pseudohypertrophic myopathy as initial manifestation of hypothyroidism. Case report. |journal=Arquivos de Neuro-psiquiatria |date=September 2003 |volume=61 |issue=3B |pages=851–4 |doi=10.1590/s0004-282x2003000500027 |pmid=14595495|doi-access=free }}
Signs and symptoms
Signs and symptoms include exercise intolerance, muscle fatigue, muscle cramps, myalgia, delayed muscle relaxation (pseudomyotonia), proximal muscle weakness, delayed deep tendon reflexes (hyporeflexia) especially of the ankles, and a pseudoathletic appearance of hypertrophic calf muscles. There may also be bradycardia, mild anemia, dry skin, hoarse voice, and cold intolerance. EMG may be normal, neuropathic, myopathic, or mixed type. Serum CK may be normal or raised. The sign of myoedema (raised muscle tissue in response to percussive tactile stimulus) may be observed. Treatment is thyroid hormone replacement therapy and prognosis is generally good. Hypertrophic calves typically return to normal after approximately 3 months of treatment.{{Cite journal |last1=Qureshi |first1=Waseem |last2=Hassan |first2=Ghulam |last3=Khan |first3=Ghulam Qadir |last4=Kadri |first4=Syed Manzoor |last5=Kak |first5=Manish |last6=Ahmad |first6=Manzoor |last7=Tak |first7=Shahid |last8=Kundal |first8=Darshan Lal |last9=Hussain |first9=Showkat |last10=Rather |first10=Abdul Rashid |last11=Masoodi |first11=Ibrahim |last12=Sikander |first12=Sabia |date=2005-07-20 |title=Hoffmann's syndrome: a case report |journal=GMS German Medical Science |volume=3 |pages=Doc05 |issn=1612-3174 |pmc=2703243 |pmid=19675722}}
Cause
It is caused by low thyroid hormones (T3 and T4).
Diagnosis
Muscle biopsy of hypothyroid myopathy shows atrophy of type II (fast-twitch/glycolytic) muscle fibres and a predominance of type I (slow-twitch/oxidative) muscle fibres; as well as abnormally high glycogen accumulation.{{Cite journal |last1=Rodolico |first1=Carmelo |last2=Bonanno |first2=Carmen |last3=Pugliese |first3=Alessia |last4=Nicocia |first4=Giulia |last5=Benvenga |first5=Salvatore |last6=Toscano |first6=Antonio |date=2020-09-01 |title=Endocrine myopathies: clinical and histopathological features of the major forms |journal=Acta Myologica |volume=39 |issue=3 |pages=130–135 |doi=10.36185/2532-1900-017 |issn=1128-2460 |pmc=7711326 |pmid=33305169}}{{Citation |last1=Fariduddin |first1=Maria M. |title=Hypothyroid Myopathy |date=2023 |url=http://www.ncbi.nlm.nih.gov/books/NBK519513/ |work=StatPearls |access-date=2023-05-28 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=30137798 |last2=Bansal |first2=Nidhi}}{{Cite journal |last1=Dimitriadis |first1=G D |last2=Leighton |first2=B |last3=Parry-Billings |first3=M |last4=West |first4=D |last5=Newsholme |first5=E A |date=1989-01-15 |title=Effects of hypothyroidism on the sensitivity of glycolysis and glycogen synthesis to insulin in the soleus muscle of the rat. |journal=Biochemical Journal |volume=257 |issue=2 |pages=369–373 |doi=10.1042/bj2570369 |issn=0264-6021 |pmc=1135589 |pmid=2649073}} The reason for the muscle hypertrophy in Hoffmann syndrome is not clearly established; it may be due to altered carbohydrate metabolism, mucoid deposits, or glycosaminoglycan deposits. In an individual diagnosed with Hoffmann syndrome whose hypertrophy did not improve after thyroid hormone replacement therapy, muscle biopsy showed hypertrophy of muscle fibres with increased nuclei, few necrotic fibres and mucoid deposits in places.
= Differential diagnoses =
Diseases known to have a pseudoathletic appearance of the calves (hypertrophy or pseudohypertrophy), including exercise intolerance and/or muscle weakness:
- Kocher–Debré–Semelaigne syndrome (childhood-onset hypothyroid myopathy),
- Glycogen storage disease (GSD-V, & late-onset GSD-II),{{Cite journal |last1=Rodríguez-Gómez |first1=I. |last2=Santalla |first2=A. |last3=Díez-Bermejo |first3=J. |last4=Munguía-Izquierdo |first4=D. |last5=Alegre |first5=L. M. |last6=Nogales-Gadea |first6=G. |last7=Arenas |first7=J. |last8=Martín |first8=M. A. |last9=Lucía |first9=A. |last10=Ara |first10=I. |date=November 2018 |title=Non-osteogenic muscle hypertrophy in children with McArdle disease |url=https://pubmed.ncbi.nlm.nih.gov/29594644/ |journal=Journal of Inherited Metabolic Disease |volume=41 |issue=6 |pages=1037–1042 |doi=10.1007/s10545-018-0170-7 |issn=1573-2665 |pmid=29594644|hdl=10578/19657 |s2cid=4394513 |hdl-access=free }}{{Cite journal |last1=Menon |first1=M. Suraj |last2=Roopch |first2=P. Sreedharan |last3=Kabeer |first3=K. Abdulkhayar |last4=Shaji |first4=C. Velayudhan |date=July 2016 |title=Calf Muscle Hypertrophy in Late Onset Pompe's Disease |url=https://journals.lww.com/armh/Fulltext/2016/04020/Calf_Muscle_Hypertrophy_in_Late_Onset_Pompe_s.22.aspx |journal=Archives of Medicine and Health Sciences |language=en-US |volume=4 |issue=2 |pages=251 |doi=10.4103/2321-4848.196188 |s2cid=58424073 |issn=2321-4848 |via=ResearchGate|doi-access=free }}
- Non-dystrophic myotonias and pseudomyotonias (such as Myotonia congenita and Brody disease),{{Cite journal |last1=Stunnenberg |first1=Bas C. |last2=LoRusso |first2=Samantha |last3=Arnold |first3=W. David |last4=Barohn |first4=Richard J. |last5=Cannon |first5=Stephen C. |last6=Fontaine |first6=Bertrand |last7=Griggs |first7=Robert C. |last8=Hanna |first8=Michael G. |last9=Matthews |first9=Emma |last10=Meola |first10=Giovanni |last11=Sansone |first11=Valeria A. |last12=Trivedi |first12=Jaya R. |last13=van Engelen |first13=Baziel G.M. |last14=Vicart |first14=Savine |last15=Statland |first15=Jeffrey M. |date=October 2020 |title=Guidelines on clinical presentation and management of nondystrophic myotonias |journal=Muscle & Nerve |volume=62 |issue=4 |pages=430–444 |doi=10.1002/mus.26887 |issn=0148-639X |pmc=8117169 |pmid=32270509}}
- Limb-girdle muscular dystrophy,{{Cite journal |last=de Visser |first=Marianne |date=2020-12-01 |title=Late-onset myopathies: clinical features and diagnosis |journal=Acta Myologica |volume=39 |issue=4 |pages=235–244 |doi=10.36185/2532-1900-027 |issn=1128-2460 |pmc=7783434 |pmid=33458579}}
- Duchenne and Becker muscular dystrophy
- Focal myositis,
- Sarcoid granulomas, and
- Amyloid deposits in muscles
Thyroid metabolism can be disrupted secondary to a primary disease. A common comorbidity of the metabolic myopathy McArdle disease (Glycogen storage disease type V) is hypothyroidism.{{Cite journal |last1=Scalco |first1=Renata S. |last2=Lucia |first2=Alejandro |last3=Santalla |first3=Alfredo |last4=Martinuzzi |first4=Andrea |last5=Vavla |first5=Marinela |last6=Reni |first6=Gianluigi |last7=Toscano |first7=Antonio |last8=Musumeci |first8=Olimpia |last9=Voermans |first9=Nicol C. |last10=Kouwenberg |first10=Carlyn V. |last11=Laforêt |first11=Pascal |last12=San-Millán |first12=Beatriz |last13=Vieitez |first13=Irene |last14=Siciliano |first14=Gabriele |last15=Kühnle |first15=Enrico |date=2020-11-24 |title=Data from the European registry for patients with McArdle disease and other muscle glycogenoses (EUROMAC) |journal=Orphanet Journal of Rare Diseases |volume=15 |issue=1 |pages=330 |doi=10.1186/s13023-020-01562-x |issn=1750-1172 |pmc=7687836 |pmid=33234167 |doi-access=free }}{{Cite journal |last1=Lucia |first1=Alejandro |last2=Martinuzzi |first2=Andrea |last3=Nogales-Gadea |first3=Gisela |last4=Quinlivan |first4=Ros |last5=Reason |first5=Stacey |last6=International Association for Muscle Glycogen Storage Disease study group |date=December 2021 |title=Clinical practice guidelines for glycogen storage disease V & VII (McArdle disease and Tarui disease) from an international study group |journal=Neuromuscular Disorders |volume=31 |issue=12 |pages=1296–1310 |doi=10.1016/j.nmd.2021.10.006 |issn=1873-2364 |pmid=34848128|s2cid=240123241 |doi-access=free }} It is also a comorbidity of late-onset Pompe disease (Glycogen storage disease type II).{{Cite journal |last1=Schneider |first1=Joseph |last2=Burmeister |first2=Lynn A. |last3=Rudser |first3=Kyle |last4=Whitley |first4=Chester B. |last5=Jarnes Utz |first5=Jeanine |date=September 2016 |title=Hypothyroidism in late-onset Pompe disease |journal=Molecular Genetics and Metabolism Reports |volume=8 |pages=24–27 |doi=10.1016/j.ymgmr.2016.06.002 |issn=2214-4269 |pmc=4932620 |pmid=27408821}}{{Cite journal |last1=Fatehi |first1=Farzad |last2=Ashrafi |first2=Mahmoud Reza |last3=Babaee |first3=Marzieh |last4=Ansari |first4=Behnaz |last5=Beiraghi Toosi |first5=Mehran |last6=Boostani |first6=Reza |last7=Eshraghi |first7=Peyman |last8=Fakharian |first8=Atefeh |last9=Hadipour |first9=Zahra |last10=Haghi Ashtiani |first10=Bahram |last11=Moravej |first11=Hossein |last12=Nilipour |first12=Yalda |last13=Sarraf |first13=Payam |last14=Sayadpour Zanjani |first14=Keyhan |last15=Nafissi |first15=Shahriar |date=2021 |title=Recommendations for Infantile-Onset and Late-Onset Pompe Disease: An Iranian Consensus |journal=Frontiers in Neurology |volume=12 |page=739931 |doi=10.3389/fneur.2021.739931 |pmid=34621239 |pmc=8490649 |issn=1664-2295 |doi-access=free }} As both hyper- and hypothyroidism disrupts muscle glycogen metabolism, it is important to keep in mind differential diagnoses and their comorbidities when trying to determine whether signs and symptoms are either primary or secondary disease.{{Cite journal |last1=Celsing |first1=F. |last2=Blomstrand |first2=E. |last3=Melichna |first3=J. |last4=Terrados |first4=N. |last5=Clausen |first5=N. |last6=Lins |first6=P. E. |last7=Jansson |first7=E. |date=April 1986 |title=Effect of hyperthyroidism on fibre-type composition, fibre area, glycogen content and enzyme activity in human skeletal muscle |url=https://pubmed.ncbi.nlm.nih.gov/2937605/ |journal=Clinical Physiology |volume=6 |issue=2 |pages=171–181 |doi=10.1111/j.1475-097x.1986.tb00066.x |issn=0144-5979 |pmid=2937605 |via=Wiley}}{{Cite journal |last=Brenta |first=Gabriela |date=2011 |title=Why can insulin resistance be a natural consequence of thyroid dysfunction? |journal=Journal of Thyroid Research |volume=2011 |pages=152850 |doi=10.4061/2011/152850 |issn=2042-0072 |pmc=3175696 |pmid=21941681 |doi-access=free }}
Management
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