gms | German Medical Science

GMS German Plastic, Reconstructive and Aesthetic Surgery – Burn and Hand Surgery

Deutsche Gesellschaft der Plastischen, Rekonstruktiven und Ästhetischen Chirurgen (DGPRÄC)
Deutsche Gesellschaft für Verbrennungsmedizin (DGV)

ISSN 2193-7052

Madelung’s disease: a man with a phenotype suggestive of anabolic steroid use

Madelung-Krankheit: Ein Mann mit einem Phänotyp, der auf den Gebrauch von anabolen Steroiden hindeutet

Case Report

  • corresponding author Georgios N. Kostopoulos - Department of Endocrinology, 424 General Military Hospital, Thessaloniki, Greece
  • Georgios G. Tzikos - Department of Surgery, 424 General Military Hospital, Thessaloniki, Greece
  • Nikolaos H. Kostogloudis - Department of Plastic Surgery, 424 General Military Hospital, Thessaloniki, Greece
  • Konstantinos A. Toulis - Department of Endocrinology, 424 General Military Hospital, Thessaloniki, Greece

GMS Ger Plast Reconstr Aesthet Surg 2020;10:Doc03

doi: 10.3205/gpras000054, urn:nbn:de:0183-gpras0000540

Veröffentlicht: 8. Dezember 2020

© 2020 Kostopoulos et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe


Madelung’s disease (MD), a rare disorder of adipose tissue, is characterized by multiple, symmetrical, non-encapsulated adipose tissue depositions in typical locations. MD typically affects middle-aged males of Mediterranean and Eastern European origin. The pathophysiology remains unknown, yet chronic alcohol consumption is frequently reported and features of metabolic syndrome are usually present. Most cases are sporadic and patients may report symptoms of compression (dysphagia, hoarseness) and/or present with a characteristic phenotypic appearance. Herein, we present a case of a 70-year-old man with a 20-year history of recurrent lipomatous formations, who had undergone several surgical procedures. His past medical and family history were unremarkable, biochemistry analysis and endocrine workup were normal, previous pathology results were indicative of benign lipomas and he reported chronic alcohol consumption. This otherwise asymptomatic patient had a very remarkable “pseudoathletic appearance”, reminiscent of anabolic steroid use. On the basis of past medical history, laboratory workup and clinical appearance, the diagnosis of MD was made and the patient was referred to the Plastic Surgery Department for further evaluation and treatment.

Keywords: Madelung’s disease, benign symmetrical lipomatosis, multiple symmetrical lipomatosis, Launois-Bensaude syndrome, lipomatosis, alcoholism


Die Madelung-Krankheit, eine seltene Erkrankung des Fettgewebes, ist charakterisiert durch multiple symmetrische Ablagerungen von Fettgewebe an typischen Körperteilen. Die Krankheit tritt hauptsächlich bei Männern im mittleren Alter auf, die aus Mittelmeerländern und osteuropäischen Ländern stammen. Die Pathogenese ist bislang unbekannt, dennoch ist die Krankheit häufig mit Alkoholmissbrauch und anderen Stoffwechselstörungen assoziiert. Die meisten Fälle treten sporadisch auf und die Patienten können Symptome einer Kompression (Dysphagie, Dysphonie) und/oder eines charakteristischen Phänotyps aufweisen. Hier präsentieren wir den Fall eines 70-jährigen Patienten, der seit 20 Jahren an rezidivierender Lipomatosis leidet und sich mehrerer chirurgischer Eingriffe unterzogen hatte. Seine Vorgeschichte war unauffällig, biochemische und endokrinologische Untersuchung waren normal. Die pathohistologische Aufarbeitung ergab die Diagnose gutartiger Lipome und der Patient berichtete über chronischen Alkoholkonsum. Dieser ansonsten asymptomatische Patient hatte ein sehr bemerkenswertes „pseudoathletisches Aussehen“, das an den Gebrauch von anabolen Steroiden erinnerte. Auf der Grundlage von Anamnese, Laboruntersuchung und klinischem Erscheinungsbild wurde die Diagnose einer Madelung-Krankheit gestellt und der Patient zur Abteilung Plastische Chirurgie überwiesen.


Madelung’s disease (MD), a rare disorder of adipose tissue, is characterized by multiple, symmetrical, non-encapsulated adipose tissue deposition in typical locations [1]. MD is also known as benign symmetrical lipomatosis or Launois-Bensaude syndrome [1] and was first described by Benjamin Brodie in 1846 [2]. In 1888, Madelung published a series of patients with symmetrical fat deposition in the submental triangle [3], while 10 years later, in 1898, Launois and Bensaude published another series of cases with similar findings [4].

MD mainly affects middle-aged males (male/female ratio 15:1) of Mediterranean and Eastern European origin [1], whereas few cases from Asia are reported as well [5]. Interestingly, it has been suggested that the silhouette of an ancient Roman statue, the Capestrano Warrior, which dates back to 6th century BC, mimics the fat distribution in MD [6]. This fact may indicate an inherited tendency in the Mediterranean region [6]. The incidence rate of the disease has been estimated as 1:25,000 men in the Italian population in 1984 [7], while the prevalence in the area of Bavaria in Germany was calculated as 1:24,274 people [8]. To the best of our knowledge, over 300 cases are described in the medical literature to date [9], [10], 106 of which were reported in a review published in 2018 [11]. The review included cases from 2000 to 2015 [11]. However, the exact number could be even higher as many undiagnosed cases may exist and therefore are not reported [1], [8].

The implicating pathogenetic mechanisms are still not well understood [1]. Although the relationship between MD and chronic alcohol consumption, especially red wine, is well known [12], cases without alcohol abuse have been described [13], [14]. It is generally believed that alcohol abuse impairs adrenergic lipolysis, leading to uncontrolled fat deposition in different areas of the body [1]. Moreover, a hypothesis that proliferation and differentiation of brown fat tissue has a key role in the pathogenesis of MD has been recently suggested [12]. Besides, mitochondrial dysfunction resulting from mutations of mitochondrial DNA has also been proposed as a trigger mechanism [15], [16].

The diagnosis of MD is based on medical history and the characteristic clinical presentation [8]. Imaging examination, such as ultrasound and magnetic resonance imaging, may be helpful; biopsy of the affected areas reveals the presence of non-encapsulated adipose tissue [1]. Herein, we present a case of a 70-year-old man with Madelung’s disease, who had recurrent fat depositions and a profound “pseudoathletic” phenotype reminiscent of anabolic steroid use.

Case description

A 70-year-old male patient was referred to the outpatient clinic for evaluation due to a 20-year history of recurrent lipomatous formations. During this 20-year period, he had undergone multiple surgical procedures but found no long-term relief. His past medical and family history were unremarkable, other than a 30-year long history of alcohol consumption. On physical examination, his body mass index was 27.3 kg/m2 and he had a symmetrical enlargement of the superior part of the trunk, including the neck, shoulder girdle, upper arms, chest and upper back, giving the patient a “pseudoathletic appearance” (Figure 1 [Fig. 1]). The lesions were soft and painless. Both testes were normal. He denied having other symptoms such as dysphagia, hoarseness, muscle weakness, decreased libido, or erectile dysfunction. Biochemistry analysis including liver function tests, lipid profile and renal function was normal. Moreover, endocrine workup (prolactin, luteinizing hormone, follicle-stimulating hormone, estradiol, testosterone, dehydroepiandrosterone sulfate, insulin-like growth factor-I, 17α-hydroxyprogesterone, cortisol, haemoglobin A1c, thyroid functions tests and autoantibodies, thyroglobulin, calcitonin) and testing for hepatitis and HIV, was also unrevealing. Finally, previous pathology results revealed benign lipomas and the diagnosis of Madelung’s disease was made.


Madelung’s disease (MD), a rare disorder of adipose tissue, is characterized by multiple, symmetrical, non-encapsulated adipose tissue deposition in typical locations, such as the cervical area, shoulders, upper trunk, upper arms, the abdomen, hips and thighs. Enzi distinguishes two types of the disease:

deposits in the area of the neck (Madelung’s collar), shoulders, supraclavicular triangle, and proximal upper limbs giving a “pseudoathletic appearance” and
deposits in the thighs and abdomen, resembling generalized obesity [7], [12].

According to Enzi’s classification system, our patient has type 1 of MD. Another classification system, developed by Donhauser et al. in 1991, categorizes patients in 3 types. Type 1 involves cases with fat distribution in the area of the neck (horsecollar), type 2 in the upper trunk and arms (pseudoathletic phenotype), and type 3 in the thighs (gynecoid type) [17], [18]. Clinical overlap between the aforementioned types may be present [18]. Recently, a novel classification based on a cohort from Germany has been proposed [8]. This comprehensive classification system divides patients with Madelung’s disease into five subtypes (Ia, Ib, Ic, II, and III). More specifically, patients with multiple lipomas in the upper body are described as type I, those with lower body involvement (thighs and legs) as type II. Type I is further subdivided in Ia (lipomas in the area of the neck), Ib (neck, shoulders and arms) and Ic (neck, shoulders, arms and trunk). If fat deposition is generalized, the patient is considered as type III [8]. Therefore, based on Donhauser’s system, our patient is type II MD while type Ic MD, if the more recent classification system is applied.

In addition, the symmetrical fat distribution in this case was quite remarkable and profound; the clinical phenotype was reminiscent of anabolic steroid use as the areas of the upper trunk and arms were involved. Anabolic steroids are in demand among athletes and bodybuilders, leading to muscle hypertrophy, proliferation and strength increase [19]. This characteristic “pseudoathletic” or “bodybuilder’s” phenotype in combination with history (Mediterranean origin and chronic alcohol abuse) and histopathological examination facilitated the diagnosis of MD.

MD is also widely known as benign symmetrical lipomatosis [1]. However, MD is not always a “benign” disorder since associated complications and comorbidities may have a negative impact on prognosis [20], [21], [22]. Patients often present features of metabolic syndrome, such as diabetes mellitus, hyperuricemia and dyslipidemia, while other cases are related to secondary liver cirrhosis, peripheral (motor or sensory) and autonomy neuropathy [1], [21], [22], [23], [24]. Neuropathy, one of the most frequent chief complaints (85% of the cases) and possibly attributed to chronic alcohol abuse, is linked with increased cardiovascular morbidity and mortality [21], [24], [25]. Hypothyroidism, chronic obstructive pulmonary disease and adrenal dysfunction are also related to MD, whereas fat depositions may occur in HIV positive patients under treatment with protease inhibitors [1], [23], [24]. Furthermore, in some cases, symptoms of compression, such as hoarseness or dysphagia, may be present due to deep infiltration in the larynx and mediastinum [1], [21], [23]. On rare occasions, malignant transformation to intramyxoid sarcoma, liposarcoma and squamous cell carcinoma has also been reported [26], [27], [28]. Notably, despite the 30-year-alcohol consumption history, our patient did not show any sign of alcohol-induced liver disease or polyneuropathy. Also he did not develop any other MD related condition or complication.

The pathogenetic background of the disease has not been fully elucidated and several hypotheses have been developed. In this case, chronic alcohol intake is believed to be the inducing factor for developing MD, as the association between alcohol and impairment of adrenergic lipolysis is well known [1]. Furthermore, most MD cases, as ours, are sporadic, but some familiar cases, inherited in an autosomal dominant manner, are reported [29]. In familiar cases, mutations in mitochondrial DNA, which have maternal origin, have been identified [15], [16], [29].

Due to the existing knowledge gap regarding the etiology of the disease, any therapeutic intervention is characterized as palliative [1]. To date, surgical resection and liposuction are the only effective therapeutic approaches, yet with high recurrence rates, as complete resection is almost impossible [1], [11]. In fact, the risk of recurrence in lipectomy has been calculated at two-thirds of the cases, while at 95% in liposuction [1]. According to a recent systematic review of case series, liposuction was associated with better aesthetic results and higher recurrence risk, whereas patients subjected to lipectomy were more likely to suffer from post-surgical complications such as infection and hemorrhage [11]. The reported recurrence rates were lower compared to the study by Szewc et al. (5 out of 95 patients (5.3%) who had undergone lipectomy; 1 out of 18 (5.6%) who had undergone liposuction and 1 out of 11 (9%) who had undergone both lipectomy and liposuction). The latter, though, might be an underestimation of the real risk, taking into account the limitations of the study. Firstly, on some occasions, patients’ records were incomplete [11]. More importantly, follow-up duration was different in each case, ranging from one week to more than thirty years [11]. In view of the aforementioned complications, the indication for surgical intervention in Madelung’s disease should be taken with care and frequently will be seen in severe cases of compression related symptoms, such as trachea or pharynx obstruction. However, cosmetic deformity can also be seen as an indication for surgery in cases in which the patient presents with a certain level of suffering from the disease [1], [30].

Pre-, peri- and postoperative strategy in cases with MD is of cardinal importance [30], [31], [32]. Endotracheal intubation due to neck immobility or presence of macroglossia may be strenuous even for experienced anesthesiologists [31]. Moreover, the risk of postoperative bleeding or hematoma should be taken into account and patients should be monitored for indicative signs or symptoms [30]. Additionally, potential respiratory depression as a consequence of oversedation should also be considered in these cases [31]. Therefore, different interventions during airway management may be warranted [30], [31], [32]. For instance, awake fiberoptic intubation or awake videolaryngoscopy could be two effective alternatives, when general anesthesia is implemented [30], [31], [32].

Unfortunately, effective pharmacological agents are not available. Apart from surgical therapy, recommendation for alcohol abstinence and lifestyle modifications should also be examined [1], [30]. In our case, the patient was referred to the Plastic Surgery Department, where long-term follow-up was recommended as no symptoms of compression were present.


In conclusion, establishing the diagnosis of MD can be challenging, since clinicians may be unaware of this condition. The presence of comorbidities should be taken into consideration during management of these patients. Surgical resection and liposuction, the only effective therapeutic approaches, are recognized as palliative treatment due to the lack of efficient pharmacological agents. Future research should focus on the pathophysiology making more treatment options available.


Competing interests

The authors declare that they have no competing interests.

Author contributions

All authors cared for the patient and contributed equally to the preparation of the manuscript. All authors approved the final manuscript.

Informed consent

The patient provided written informed consent for publication of this case.


Szewc M, Sitarz R, Moroz N, Maciejewski R, Wierzbicki R. Madelung’s disease – progressive, excessive, and symmetrical deposition of adipose tissue in the subcutaneous layer: case report and literature review. Diabetes Metab Syndr Obes. 2018;11:819-25. DOI: 10.2147/DMSO.S181154 Externer Link
Brodie BC. Clinical Lectures on Surgery delivered at St. George’s Hospital. Am J Med Sci. 1846;11(22):437. DOI: 10.1097/00000441-184604000-00028 Externer Link
Madelung OW. Ueber den Fetthals. Arch Klin Chir. 1888;37:106-30.
Launois PE, Bensaude R. De l’adenolipomatose symetriqe. Bull Mem Soc Med Hop Paris. 1898;1:298.
Chuang CC, Cheng YF, Chang HP, Lin CZ. Madelung’s disease. J Chin Med Assoc. 2004 Nov;67(11):591-4.
Feliciani C, Amerio P. Images in clinical medicine. Madelung’s disease: inherited from an ancient Mediterranean population? N Engl J Med. 1999 May;340(19):1481. DOI: 10.1056/NEJM199905133401906 Externer Link
Enzi G. Multiple symmetric lipomatosis: an updated clinical report. Medicine (Baltimore). 1984 Jan;63(1):56-64. DOI: 10.1097/00005792-198401000-00004 Externer Link
Schiltz D, Anker A, Ortner C, Tschernitz S, Koller M, Klein S, Felthaus O, Schreml J, Schreml S, Prantl L. Multiple Symmetric Lipomatosis: New Classification System Based on the Largest German Patient Cohort. Plast Reconstr Surg Glob Open. 2018 Apr;6(4):e1722. DOI: 10.1097/GOX.0000000000001722 Externer Link
Wan SC, Huang MH, Perng CK, Liao WC. Madelung Disease: Analysis of Clinicopathological Experience in Taipei Veterans General Hospital. Ann Plast Surg. 2019 Jan;82(1S Suppl 1):S66-S71. DOI: 10.1097/SAP.0000000000001719 Externer Link
Multiple symmetric lipomatosis. In: Orphanet. [last updated 2019 Oct]. Available from: Externer Link
Chen CY, Fang QQ, Wang XF, Zhang MX, Zhao WY, Shi BH, Wu LH, Zhang LY, Tan WQ. Madelung's Disease: Lipectomy or Liposuction? Biomed Res Int. 2018;2018:3975974. DOI: 10.1155/2018/3975974 Externer Link
Enzi G, Busetto L, Sergi G, Coin A, Inelmen EM, Vindigni V, Bassetto F, Cinti S. Multiple symmetric lipomatosis: a rare disease and its possible links to brown adipose tissue. Nutr Metab Cardiovasc Dis. 2015 Apr;25(4):347-53. DOI: 10.1016/j.numecd.2015.01.010 Externer Link
Bergler-Czop B, Wcisło-Dziadecka D, Brzezińska-Wcisło L. Madelung’s disease in a patient with chronic renal insufficiency: a case report and review of literature. Postepy Dermatol Alergol. 2014 May;31(2):121-4. DOI: 10.5114/pdia.2014.40922 Externer Link
El Ouahabi H, Doubi S, Lahlou K, Boujraf S, Ajdi F. Launois-bensaude syndrome: A benign symmetric lipomatosis without alcohol association. Ann Afr Med. 2017 Jan-Mar;16(1):33-4. DOI: 10.4103/1596-3519.202082 Externer Link
Gámez J, Playán A, Andreu AL, Bruno C, Navarro C, Cervera C, Arbós MA, Schwartz S, Enriquez JA, Montoya J. Familial multiple symmetric lipomatosis associated with the A8344G mutation of mitochondrial DNA. Neurology. 1998 Jul;51(1):258-60. DOI: 10.1212/wnl.51.1.258 Externer Link
López-Gallardo E, Cammarata-Scalisi F, Emperador S, Hernández-Ainsa C, Habbane M, Vela-Sebastián A, Bayona-Bafaluy MP, Montoya J, Ruiz-Pesini E. Mitochondrial DNA pathogenic mutations in multiple symmetric lipomatosis. Clin Genet. 2020 May;97(5):731-5. DOI: 10.1111/cge.13701 Externer Link
Donhauser G, Vieluf D, Ruzicka T, Braun-Falco O. Benigne symmetrische Lipomatose Launois-Bensaude Typ III und Bureau-Barrière-Syndrom [Benign symmetric Launois-Bensaude type III lipomatosis and Bureau-Barrière syndrome]. Hautarzt. 1991 May;42(5):311-4.
Pinto CI, Carvalho PJ, Correia MM. Madelung’s Disease: Revision of 59 Surgical Cases. Aesthetic Plast Surg. 2017 Apr;41(2):359-68. DOI: 10.1007/s00266-016-0759-x Externer Link
Kicman AT. Pharmacology of anabolic steroids. Br J Pharmacol. 2008 Jun;154(3):502-21. DOI: 10.1038/bjp.2008.165 Externer Link
Suito M, Kitazawa T, Takashimizu I, Ikeda T. Madelung’s disease: long-term follow-up. J Surg Case Rep. 2019 Jan;2019(1):rjy356. DOI: 10.1093/jscr/rjy356 Externer Link
Yeh NC, Yang CY, Chou CW, Yen FC, Lee SY, Tien KJ. Madelung’s disease. J Clin Endocrinol Metab. 2012 Sep;97(9):3012-3. DOI: 10.1210/jc.2012-1649 Externer Link
Enzi G, Busetto L, Ceschin E, Coin A, Digito M, Pigozzo S. Multiple symmetric lipomatosis: clinical aspects and outcome in a long-term longitudinal study. Int J Obes Relat Metab Disord. 2002 Feb;26(2):253-61. DOI: 10.1038/sj.ijo.0801867 Externer Link
Brea-García B, Cameselle-Teijeiro J, Couto-González I, Taboada-Suárez A, González-Álvarez E. Madelung’s disease: comorbidities, fatty mass distribution, and response to treatment of 22 patients. Aesthetic Plast Surg. 2013 Apr;37(2):409-16. DOI: 10.1007/s00266-012-9874-5 Externer Link
Bucciarelli M, Fan C. Diffuse symmetrical Lipomatosis: a case report depicting the potential for severity. AACE Clinical Case Reports. 2017;3(4):e370-3. DOI: 10.4158/EP161546.CR Externer Link
Fonseca VR, Freitas C, Palmeira M, Ferreira C, Victorino R. Cardiac noradrenergic denervation in a patient with multiple symmetric lipomatosis. Cardiology. 2012;121(3):160-3. DOI: 10.1159/000336951 Externer Link
Tizian C, Berger A, Vykoupil KF. Malignant degeneration in Madelung’s disease (benign lipomatosis of the neck): case report. Br J Plast Surg. 1983 Apr;36(2):187-9. DOI: 10.1016/0007-1226(83)90089-9 Externer Link
Chan ES, Ahuja AT, King AD, Lau WY. Head and neck cancers associated with Madelung’s disease. Ann Surg Oncol. 1999 Jun;6(4):395-7. DOI: 10.1007/s10434-999-0395-7 Externer Link
Borriello M, Lucidi A, Carbone A, Iannone V, Ferrandina G. Malignant transformation of Madelung’s disease in a patient with a coincidental diagnosis of breast cancer: a case report. Diagn Pathol. 2012 Sep;7:116. DOI: 10.1186/1746-1596-7-116 Externer Link
Zolotov S, Xing C, Mahamid R, Shalata A, Sheikh-Ahmad M, Garg A. Homozygous LIPE mutation in siblings with multiple symmetric lipomatosis, partial lipodystrophy, and myopathy. Am J Med Genet A. 2017 Jan;173(1):190-4. DOI: 10.1002/ajmg.a.37880 Externer Link
Stopar T, Novak Jankovic V, Casati A. Four different airway-management strategies in patient with Launois-Bensaude syndrome or Madelung’s disease undergoing surgical excision of neck lipomatosis with a complicated postoperative course. J Clin Anesth. 2005 Jun;17(4):300-3. DOI: 10.1016/j.jclinane.2004.07.007 Externer Link
Becerra-Bolaños Á, Valencia L, Cabrera-Ramírez L, Rodríguez-Pérez A. Madelung’s Disease and Airway Management. Anesthesiology. 2019 Feb;130(2):313. DOI: 10.1097/ALN.0000000000002487 Externer Link
Stopar-Pintaric T, Markova L, Tomazevic M, Hodzovic I. An awake videolaryngoscope-assisted intubation in a patient with Madelung disease and a critical airway obstruction. Minerva Anestesiol. 2017 Jun;83(6):660-2. DOI: 10.23736/S0375-9393.16.11510-X Externer Link