Three Cases of Androgen-Dependent Disease Associated with Myotonic

JEADV (2003) 17, 56–58 CASE REPORT

BlackwellThree Science, Ltd cases of androgen-dependent disease associated with myotonic dystrophy

SM Cooper,†* RPR Dawber,† D Hilton-Jones‡ †Department of Dermatology, Oxford Radcliffe Hospitals, Oxford, OX3 7LJ, UK, ‡Muscle and Nerve Centre, Radcliffe Inﬁrmary, Oxford, OX2 6HE, UK. *Corresponding author, Department of Dermatology, Churchill Hospital, Headington, Oxford, OX3 7LJ, UK, tel. +01865 228232; fax +1865 228240

ABSTRACT Three cases of androgen-dependent disease in females with myotonic dystrophy are described. Serum androgens in individuals affected by myotonic dystrophy are known to be lower on average than in normal controls. Despite this these three females developed diseases that are androgen dependent, including acne, hidradenitis suppurativa, androgenetic alopecia and keratosis pilaris. These cases support the hypothesis that the peripheral response to androgens rather than absolute circulating levels of androgens is important in androgen-dependent conditions. Key words: androgenetic alopecia, androgens, hidradenitis suppurativa, keratosis pilaris, myotonic dystrophy

Received: 29 December 2000, accepted 5 February 2002

Myotonic dystrophy (Steinert’s disease) is the commonest form of muscular dystrophy in adults, with an estimated incidence of Case reports 1 in 8000. It is inherited as an autosomal dominant trait and Case 1 caused by an unstable expansion of a trinucleotide (CTG) repeat in the untranslated region of the dystrophia myotonica A 43-year-old woman with myotonic dystrophy developed protein kinase gene on chromosome 19q13.3.1 Age of onset and slowly progressive thinning of hair over the vertex, in an severity correlate with the size of the expansion.2 The expansion androgenetic distribution, in her third decade. The hair was is unstable and tends to increase in size on transmission, giving diffusely thin (Ludwig pattern type II) with retention of the rise to the phenomenon of anticipation, in which disease frontal hairline (fig. 2). The scalp was normal with no evidence severity increases in successive generations. of scarring and the hair shafts were normal. She had no other Classical onset myotonic dystrophy is a multisystem disease.3 virilizing features and was otherwise well with no previous In addition to skeletal muscle features (facial and anterior neck endocrine problems. She was diagnosed with myotonic muscle wasting and weakness, ptosis, early distal limb weakness dystrophy at the age of 34, the diagnosis only being suspected and myotonia) endocrine features include premature balding, when she presented to an ophthalmologist with a presenile testicular atrophy and insulin resistance. Systemic features cataract. The diagnosis of myotonic dystrophy was confirmed by include presenile cataracts, cardiac conduction defects, exces- the presence of an expansion of approximately 633 repeats. She sive daytime sleepiness and reduced IQ. The combination of is mildly affected by myotonic dystrophy. Endocrine investigations, facial muscle involvement and premature balding gives rise to including sex hormone binding globulin (SHBG), follicle- the characteristic facial appearance (fig. 1). stimulating hormone (FSH), luteinizing hormone (LH), We report three cases of females affected by myotonic dystro- prolactin, ferritin and thyroid function were normal and serum phy in whom androgen-dependent diseases were diagnosed. testosterone was at the lower end of the normal range. Circulating androgens are decreased in myotonic dystrophy compared with normal controls.4 These cases provide import- Case 2 ant clinical evidence for abnormalities of end-organ sensitivity to androgens in myotonic dystrophy and also provide insight A 37-year-old woman with myotonic dystrophy had a 20-year into the mechanism of other androgen-dependent diseases. history of recurrent, suppurating boils in the groins and

Androgen-dependent disease associated with myotonic dystrophy 57

fig. 2 Vertical thinning with preservation of the frontal margin.

fig. 1 Typical myotonic facies. Note the frontal recession. thighs. Horny follicular papules with variable perifollicular erythema were observed consistent with keratosis pilaris. axillae. Examination findings included grouped comedones, Her myotonic dystrophy was severe and she had learning scarring and boils consistent with a diagnosis of hidradenitis difficulties. suppurativa. She had been treated with long courses of antibiotics, topical antiseptics and Dianette® (cyproterone acetate 2 mg, ethinyloestradiol 35 µg) with limited benefit only. Discussion Frontal balding was observed, but hair was normal over the We present three women with known androgen-dependent vertex. She had extensive horny follicular papules on the upper conditions in the setting of a disease associated with low arms, typical of keratosis pilaris, but there were no other circulating androgens. Carter and Steinbeck found that serum virilizing features. She had severe myotonia, marked facial DHEA and dehydroepiandosterone sulphate (DHEAS), the wasting and weakness, and limited mobility. Genetic studies most abundant circulating androgens, were significantly lower confirmed she carried an expansion of approximately 1400 than controls in 19 affected male and female patients.5 repeats. Endocrine investigations, including SHBG, FSH, LH, Johansson et al.6 confirmed significantly lower DHEA, DHEAS prolactin, androstenedione, ferritin and thyroid function were and 17α-hydroxyprogesterone in a further 15 males. normal but serum dehydroepiandosterone (DHEA) and serum Our three cases all demonstrate androgen-dependent testosterone were below the normal range. diseases: male-pattern alopecia, hidradenitis suppurativa, keratosis pilaris and acne. The evidence for androgen dependence of acne and male pattern baldness comes from the response to Case 3 treatment with antiandrogens and the development of acne A 37-year-old female, severely affected by congenital myotonic after puberty. In addition, androgenetic alopecia in males does dystrophy, was noted to have papules, pustules and comedones not occur in eunuchs and hirsutism does not occur in males or over the trunk and face typical of acne vulgaris. She had females with absent androgens. Keratosis pilaris was first extensive rough areas on the upper outer arms and upper proposed as an androgen-dependent disorder by Barth et al.7

58 Cooper et al.

who found an increased incidence and severity of keratosis pilaris disruption of intranuclear pathways.1 It is possible that intra- in hyperandrogenized, obese subjects. They proposed the under- nuclear pathways for androgen binding may be affected. lying cause to be hyperkeratinization of the pilosebaceous unit of terminal hairs in response to androgens, akin to the response of the infundibulum of the pilosebaceous unit in acne. Sawers References et al.8 demonstrated that an antiandrogen, cyproterone acetate, 1 Brook JD, McCurrach ME, Harley HG et al. Molecular basis of effectively inhibited hidradenitis. Finasteride, a selective inhibitor myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at of the 5-α reductase type II isoenzyme, has been effective in treating the 3′ end of a transcript encoding a protein kinase family member. two females with severe, long-standing hidradenitis.9 Cell 1992; 68: 799–808. The presence of androgen-dependent disease in subjects with 2 Harley HG, Brook JD, Rundle SA et al. Expansion of an unstable myotonic dystrophy in whom androgens tend to be lower than DNA region and phenotypic variation in myotonic dystrophy. normal is evidence that the peripheral response to androgens is Nature 1992; 355: 545–546. more important than absolute circulating levels. In many of the 3 Harper PS. Myotonic dystrophy, 2nd edn. Saunders, London, 1989. androgen-dependent diseases circulating androgens are often 4 Harper PS. Endocrine abnormalities in myotonic dystrophy. In: normal or only modestly elevated. Barth et al.10 found no evidence Myotonic dystrophy, 2nd edn. Saunders, London, 1989: 121–148. for biochemical hyperandrogenism in 66 women with hidradenitis 5 Carter JN, Steinbeck KS. Reduced adrenal androgens in patients suppurativa when compared with age- and weight-matched with myotonic dystrophy. J Clin Endocrinol Metab 1985; 60: controls. If absolute levels of androgens were important, one 611–614. would expect a much higher incidence of acne and hidradenitis 6 Johansson A, Henriksson A, Olofsson BO et al. Adrenal steroid in males in whom circulating levels are higher. In fact, in dysregulation in dystrophia myotonica. J Intern Med 1999; 245: hidradenitis, there is marked female excess. 345–351. An alternative explanation is that androgens are irrelevant in 7 Barth JH, Wojnarowska F, Dawber RPR. Is keratosis pilaris another the so-called androgen-mediated diseases. The response to androgen-dependent dermatosis? Clin Exper Derm 1988; 13: treatment of these conditions with antiandrogens suggests 240–241. otherwise. It is therefore likely that there is a difference in the 8 Sawers RS, Randall VA, Ebling FJG. Control of hidradenitis peripheral response to androgens between individuals, mediated suppurativa. Br J Dermatol 1986; 141: 1138–1139. by peripheral androgen receptors, and that absolute levels of 9 Farrell AM, Randall VM, Vafaee T et al. Finasteride as a therapy for circulating androgens are of limited importance. We speculate hidradenitis suppurativa. Br J Dermatol 1999; 141: 1138–1139. that there is a functional difference in receptors accounting for 10 Barth JH, Layton AM, Cunliffe WJ. Endocrine factors in pre- and the frontal balding in myotonic dystrophy. The molecular basis postmenopausal women with hidradenitis suppurativa. Br J of myotonic dystrophy remains uncertain, but may involve Dermatol 1996; 134: 1057–1059.

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