Kocher–Debre–Semelaigne syndrome explained

Kocher–Debré–Semelaigne syndrome
Synonyms:Debré–Semelaigne syndrome, cretinism-muscular hypertrophy, hypothyroidism-large muscle syndrome, hypothyreotic muscular hypertrophy in children, infantile myxoedema-muscular hypertrophy, myopathy-myxoedema syndrome, myxoedema-muscular hypertrophy syndrome, myxoedema-myotonic dystrophy syndrome, muscular pseudohypertrophy-hypothyroidism syndrome

Kocher–Debré–Semelaigne syndrome (KDSS) is hypothyroidism in infancy or childhood characterised by lower extremity or generalized muscular hypertrophy (Herculean appearance[1]), myxoedema, short stature, and cognitive impairment.[2]

The syndrome is named after Emil Theodor Kocher, Robert Debré and Georges Semelaigne. Also known as Debré–Semelaigne syndrome or cretinism-muscular hypertrophy, hypothyroid myopathy, hypothyroidism-large muscle syndrome, hypothyreotic muscular hypertrophy in children, infantile myxoedema-muscular hypertrophy, myopathy-myxoedema syndrome, myxoedema-muscular hypertrophy syndrome, myxoedema-myotonic dystrophy syndrome.

The adult-onset form of this syndrome is Hoffmann syndrome.[3] Some sources claim that two of the differentiating symptoms between KDSS and Hoffmann syndrome is that Hoffmann syndrome lacks painful spasms and pseudomyotonia;[4] however, this claim is in conflict with other sources that list these symptoms as also being present in Hoffmann syndrome.[5] [6] [7] [8]

Presentation

The age at which a child presents with KDSS may vary from new born to as late as 11 years of age. This disease is very rare as only less than 10% of children with hypothyroid myopathy develops this condition. Along with features of hypothyroidism (such as lethargy, slow heart rate, cold intolerance, dry skin, and hoarse voice) the main additional feature is muscle hypertrophy. It can happen in any muscle of the limbs, but commonly affects the calf muscles, giving the typical Herculean appearance.[9]

Other features are pseudomyotonia, myokymia, slow tendon reflex, slowed muscle contractions and relaxations, muscle stiffness, proximal muscle weakness and myopathy. The severity of these symptoms are determined by the period of hypothyroidism and the degree of deficiency of thyroid hormones.[10] It may also include macroglossia.[11]

EMG is either normal or may show myopathic low amplitude and short duration motor unit action potentials (MUAPS).[12] The enzymes creatine kinase is elevated usually.

Pathophysiology

The assumed cause of muscle hypertrophy in KDSS is an abnormal metabolism of carbohydrates leading to increased glycogen accumulation and increased mucopolysaccharide deposits in the muscles.[13] Yet another speculation is an excess intra cellular calcium due to ineffective reuptake into the sarcoplasmic reticulum, which causes a sustained contraction and thereby hypertrophy.[14]

In hypothyroidism the fast twitch muscle fiber is converted to slow twitch fiber, causing the slower reflex or hung up reflex. This may occur as a result of reduction in muscle mitochondrial oxidative capacity and beta-adrenergic receptors, as well as the induction of an insulin-resistant state, due to decrease in thyroid hormones.[15]

The causes for muscle weakness is said to be decrease in muscle carnitine, decreased muscle oxidation, expression of a slower ATPase in myosin chain and decreased transport across the cell membrane.[16] [17]

The rigidity associated with congenital hypothyroidism may be due to abnormal development of basal ganglia.[18]

Differential diagnoses

Diseases known to have a pseudoathletic appearance of the calves (hypertrophy or pseudohypertrophy), including exercise intolerance and/or muscle weakness:

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.[23] [24] It is also a comorbidity of late-onset Pompe disease (Glycogen storage disease type II).[25] [26] 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.[27] [28] [29] [30]

Treatment

The muscle hypertrophy and other symptoms are reversible on treatment with levothyroxine.[31]

Notes and References

  1. Book: Sainani . JP . Clinical Cases & Pearls in Medicine . 2015 . JP Medical Ltd. . 9789351526469 . 333.
  2. Book: Millichap. J. Gordon. Neurological syndromes : a clinical guide to symptoms and diagnosis. 2013. Springer New York. New York, NY. 9781461477860. 121.
  3. Book: Bhansali . Anil . Clinical Rounds in Endocrinology: Volume II - Pediatric Endocrinology . Aggarwal . Anuradha . 2016 . Springer . 9788132228158 . 81.
  4. Agrawal . Sanwar . Thakur . Prashant . 2010-12-16 . Kocher–Debré–Semelaigne syndrome . BMJ Case Reports . 2010 . bcr0420102877 . 10.1136/bcr.04.2010.2877 . 1757-790X . 3029797 . 22802324.
  5. Vasconcellos . Luiz Felipe Rocha . Peixoto . Maria Claudia . de Oliveira . Tatiana Nunes . Penque . Glória . Leite . Ana Claudia Celestino . September 2003 . Hoffman's syndrome: pseudohypertrophic myopathy as initial manifestation of hypothyroidism. Case report . Arquivos de Neuro-Psiquiatria . 61 . 3B . 851–854 . 10.1590/s0004-282x2003000500027 . 0004-282X . 14595495. free .
  6. Mangaraj . Swayamsidha . Sethy . Ganeswar . 2014 . Hoffman's syndrome – A rare facet of hypothyroid myopathy . Journal of Neurosciences in Rural Practice . 5 . 4 . 447–448 . 10.4103/0976-3147.140025 . 0976-3147 . 4173264 . 25288869 . free .
  7. Udayakumar . N. . Rameshkumar . A. C. . Srinivasan . A. V. . 2005 . Hoffmann syndrome: presentation in hypothyroidism . Journal of Postgraduate Medicine . 51 . 4 . 332–333 . 0022-3859 . 16388183.
  8. Qureshi . Waseem . Hassan . Ghulam . Khan . Ghulam Qadir . Kadri . Syed Manzoor . Kak . Manish . Ahmad . Manzoor . Tak . Shahid . Kundal . Darshan Lal . Hussain . Showkat . Rather . Abdul Rashid . Masoodi . Ibrahim . Sikander . Sabia . 2005-07-20 . Hoffmann's syndrome: a case report . GMS German Medical Science . 3 . Doc05 . 1612-3174 . 2703243 . 19675722.
  9. Tullu. Milind S.. Udgirkar. Vardhaman S.. Muranjan. Mamta N.. Sathe. Shefali A.. Kamat. Jaishree R.. 2003-08-01. Kocher-Debre-Semelaigne syndrome: Hypothyroidism with muscle pseudohypertrophy. The Indian Journal of Pediatrics. en. 70. 8. 671–673. 10.1007/BF02724260. 14510090 . 40709054 . 0973-7693.
  10. Klein. Irwin. Mantell. Paul. Parker. Mitchell. Levey. Gerald S.. May 1980. Resolution of abnormal muscle enzyme studies in hypothyroidism. The American Journal of the Medical Sciences. en. 279. 3. 159–162. 10.1097/00000441-198005000-00004. 7424961. 11587035.
  11. Shaw . Chandan . Shaw . Prachi . 2012 . Kocher-Debre-Semelaigne Syndrome: Hypothyroid Muscular Pseudohypertrophy—A Rare Report of Two Cases . Case Reports in Endocrinology . 2012 . 153143 . 10.1155/2012/153143 . 2090-6501 . 3420572 . 22934196 . free .
  12. Rajvanshi. Satyam. Rai. GopalK. Philip. Rajeev. Gupta. KK. 2012. Kocher-Debre-Semelaigne syndrome. Thyroid Research and Practice. 9. 2. 53. 10.4103/0973-0354.96047. 0973-0354 . free .
  13. Panat. Sunil R.. Jha. Prakash Chandra. Chinnannavar. Sangamesh N.. Chakarvarty. Ankkita. Aggarwal. Ashish. March 2013. Kocher Debre Semelaigne Syndrome: A Rare Case Report with Orofacial Manifestations. Oman Medical Journal. 28. 2. 128–130. 10.5001/omj.2013.33. 1999-768X. 3628204. 23599883.
  14. Pourmand. Rahman. Metabolic Myopathies. February 2000. Neurologic Clinics. 18. 1. 1–13. 10.1016/s0733-8619(05)70176-6. 10658166. 0733-8619.
  15. Benvenga. Salvatore. Toscano. Antonio. Rodolico. Carmelo. Vita. Giuseppe. Trimarchi. Francesco. August 2001. Endocrine Evaluation for Muscle Pain. Journal of the Royal Society of Medicine. 94. 8. 405–407. 10.1177/014107680109400810. 11461987. 1281637. 0141-0768. free.
  16. Horak. Holli A.. Pourmand. Rahman. Endocrine Myopathies. February 2000. Neurologic Clinics. 18. 1. 203–213. 10.1016/s0733-8619(05)70186-9. 10658176. 0733-8619.
  17. Sinclair. Christopher. Gilchrist. James M.. Hennessey. James V.. Kandula. Manju. 2005. Muscle carnitine in hypo- and hyperthyroidism. Muscle & Nerve. 32. 3. 357–359. 10.1002/mus.20336. 15803480. 41839983 . 0148-639X.
  18. Book: Barrett, Kim E.. Ganong's review of medical physiology. Barman, Susan M.,, Brooks, Heddwen L.,, Yuan, Jason X.-J., 1963-, Preceded by: Ganong, William F.. 9781260122404. Twenty-sixth. [New York]. 848. 1076268769. 2019-01-29.
  19. Rodríguez-Gómez . I. . Santalla . A. . Díez-Bermejo . J. . Munguía-Izquierdo . D. . Alegre . L. M. . Nogales-Gadea . G. . Arenas . J. . Martín . M. A. . Lucía . A. . Ara . I. . November 2018 . Non-osteogenic muscle hypertrophy in children with McArdle disease . Journal of Inherited Metabolic Disease . 41 . 6 . 1037–1042 . 10.1007/s10545-018-0170-7 . 1573-2665 . 29594644. 10578/19657 . 4394513 . free .
  20. Menon . M. Suraj . Roopch . P. Sreedharan . Kabeer . K. Abdulkhayar . Shaji . C. Velayudhan . July 2016 . Calf Muscle Hypertrophy in Late Onset Pompe's Disease . Archives of Medicine and Health Sciences . en-US . 4 . 2 . 251 . 10.4103/2321-4848.196188 . 58424073 . 2321-4848. free .
  21. Stunnenberg . Bas C. . LoRusso . Samantha . Arnold . W. David . Barohn . Richard J. . Cannon . Stephen C. . Fontaine . Bertrand . Griggs . Robert C. . Hanna . Michael G. . Matthews . Emma . Meola . Giovanni . Sansone . Valeria A. . Trivedi . Jaya R. . van Engelen . Baziel G.M. . Vicart . Savine . Statland . Jeffrey M. . October 2020 . Guidelines on clinical presentation and management of nondystrophic myotonias . Muscle & Nerve . 62 . 4 . 430–444 . 10.1002/mus.26887 . 0148-639X . 8117169 . 32270509.
  22. de Visser . Marianne . 2020-12-01 . Late-onset myopathies: clinical features and diagnosis . Acta Myologica . 39 . 4 . 235–244 . 10.36185/2532-1900-027 . 1128-2460 . 7783434 . 33458579.
  23. Lucia . Alejandro . Martinuzzi . Andrea . Nogales-Gadea . Gisela . Quinlivan . Ros . Reason . Stacey . International Association for Muscle Glycogen Storage Disease study group . December 2021 . Clinical practice guidelines for glycogen storage disease V & VII (McArdle disease and Tarui disease) from an international study group . Neuromuscular Disorders . 31 . 12 . 1296–1310 . 10.1016/j.nmd.2021.10.006 . 1873-2364 . 34848128. 240123241 . free .
  24. Scalco . Renata S. . Lucia . Alejandro . Santalla . Alfredo . Martinuzzi . Andrea . Vavla . Marinela . Reni . Gianluigi . Toscano . Antonio . Musumeci . Olimpia . Voermans . Nicol C. . Kouwenberg . Carlyn V. . Laforêt . Pascal . San-Millán . Beatriz . Vieitez . Irene . Siciliano . Gabriele . Kühnle . Enrico . 2020-11-24 . Data from the European registry for patients with McArdle disease and other muscle glycogenoses (EUROMAC) . Orphanet Journal of Rare Diseases . 15 . 1 . 330 . 10.1186/s13023-020-01562-x . 1750-1172 . 7687836 . 33234167 . free .
  25. Schneider . Joseph . Burmeister . Lynn A. . Rudser . Kyle . Whitley . Chester B. . Jarnes Utz . Jeanine . 2016-07-01 . Hypothyroidism in late-onset Pompe disease . Molecular Genetics and Metabolism Reports . 8 . 24–27 . 10.1016/j.ymgmr.2016.06.002 . 2214-4269 . 4932620 . 27408821.
  26. Fatehi . Farzad . Ashrafi . Mahmoud Reza . Babaee . Marzieh . Ansari . Behnaz . Beiraghi Toosi . Mehran . Boostani . Reza . Eshraghi . Peyman . Fakharian . Atefeh . Hadipour . Zahra . Haghi Ashtiani . Bahram . Moravej . Hossein . Nilipour . Yalda . Sarraf . Payam . Sayadpour Zanjani . Keyhan . Nafissi . Shahriar . 2021-09-21 . Recommendations for Infantile-Onset and Late-Onset Pompe Disease: An Iranian Consensus . Frontiers in Neurology . 12 . 739931 . 10.3389/fneur.2021.739931 . 1664-2295 . 8490649 . 34621239 . free .
  27. Rodolico . Carmelo . Bonanno . Carmen . Pugliese . Alessia . Nicocia . Giulia . Benvenga . Salvatore . Toscano . Antonio . 2020-09-01 . Endocrine myopathies: clinical and histopathological features of the major forms . Acta Myologica . 39 . 3 . 130–135 . 10.36185/2532-1900-017 . 1128-2460 . 7711326 . 33305169.
  28. Dimitriadis . G D . Leighton . B . Parry-Billings . M . West . D . Newsholme . E A . 1989-01-15 . Effects of hypothyroidism on the sensitivity of glycolysis and glycogen synthesis to insulin in the soleus muscle of the rat. . Biochemical Journal . 257 . 2 . 369–373 . 10.1042/bj2570369 . 0264-6021 . 1135589 . 2649073.
  29. Celsing . F. . Blomstrand . E. . Melichna . J. . Terrados . N. . Clausen . N. . Lins . P. E. . Jansson . E. . April 1986 . Effect of hyperthyroidism on fibre-type composition, fibre area, glycogen content and enzyme activity in human skeletal muscle . Clinical Physiology . 6 . 2 . 171–181 . 10.1111/j.1475-097x.1986.tb00066.x . 0144-5979 . 2937605.
  30. Brenta . Gabriela . 2011 . Why Can Insulin Resistance Be a Natural Consequence of Thyroid Dysfunction? . Journal of Thyroid Research . 2011 . 152850 . 10.4061/2011/152850 . 2090-8067 . 3175696 . 21941681 . free .
  31. Mehrotra. P. 2002-03-01. Kocher Debre Semelaigne syndrome: regression of pesudohypertrophy of muscles on thyroxine. Archives of Disease in Childhood. 86. 3. 224a–224. 10.1136/adc.86.3.224-a. 11861255. 1719134. 0003-9888.

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