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On-line version ISSN 1806-4841
An. Bras. Dermatol. vol.79 no.4 Rio de Janeiro July/Aug. 2004
Dermatologic aspects in acromegaly*
Maurício ZaniniI; Renata Rodrigues OshiroII; Luiz Henrique Camargo PaschoalIII; Francisco Macedo PaschoalIV; Fábio R. TimonerV
IDermatology Specialist title with
the Brazilian Society of Dermatology Supervisor in Dermatological Surgery and
IISpecialist in Dermatology by the Brazilian Dermatology Society (SBD)
IIIPh.D. in Dermatology. Director of Medical Faculty of ABC
IVPh.D. in Dermatology. Assistant Professor of Dermatology
VMaster's Degree candidate in Dermatology. Assistant Professor of Dermatology
Acromegaly is a rare endocrine syndrome characterized by mesenchymal hyperplasia. Its manifestation is usually extremely insidious. As it precociously develops with cutaneous alterations, the dermatologist is often the first medical professional to be sought by the patient. The authors describe the dermatologic and clinical findings of this disease.
Key words: acromegaly; adenoma; growth hormone.
Acromegaly is a rare endocrine syndrome characterized by mesenchymal hyperplasia. The clinical condition is systemic and its course insidious. Cutaneous manifestations are precocious. When associated with other alterations, they allow the dermatologist to diagnose this affection.1 This paper describes the clinical and dermatological findings of acromegaly.
Acromegalic syndrome results from an excess of growth hormones, produced by a previous case of hypophysis. Its biological action is measured by somatomedines, i.e. insuline-like growth factors whose production is stimulated by hepatic tissue.1,2 Ninety percent or more of cases are sporadic and result from generally benign hypophysis macroadenoma. These tumors customarily arise in patients ranging from 30 to 50 years of age. In some patients, the condition results from pancreatic and lung tumors, producers of the hypothalamic hormone responsible for releasing the growth hormone.2
Acromegaly progresses very slowly and is installed in an extremely insidious manner. Its clinical manifestations may be divided didactically into general cases and dermatologic ones. Acromegaly includes mesenchymal hyperplasia - the growth hormone, mediated by somatomedines, determines hypertrophy of the conjunctive tissue, especially at the expense of glycosaminoglicans mucopolyssacharides. A degree of controversy remains as to whether an increased occurrence of colagen and higher interstitial hydric retension should be included in this group. The conjunctive bone tissue is also involved. The skin and its annexes show hyperplasia, as well.3,4,5 It may be associated with multiple endocrine neoplasia type I, McCune-Albright syndrome (nevum spilus, café-au-lait spots) and Carney's syndrome (atrial mixoma, acoustic neuroma and spotted pigmentation).6
The main clinical aspect of this affliction is the elongation or intumescence of the cartilaginous tissue and acral bone ('acro' means acral or extremity, while 'megaly' refers to huge or gigantic). Fingers, hands and feet show an increase in size. The patient gradually feels the need to increase shoe and ring sizes. A very characteristic case is acromegaloid facial appearance syndrome, featuring a prominent forehead, prognasthism (mandibular protusion), enlarged nose, large ears, macroglossia, (usually lower) macrocheilia, hypertelorism, palpebral edema and clenching of the teeth due to gengival hyperplasia.1,2,6,7
Cutaneous manifestations include: (1) increase in cutaneous thickness and salience of the creases and wrinkles; (2) increase in ecrine and aprocrine perspiration, frequently occuring along with bromidosis; (3) increase in sebaceous secretion; (4) in the initial phases, hypertricosis and/or hirsutism; later phases include a tendency to rarefaction and miniaturization of skin hair; and (5) nails frequently with pachonychia and platonychia.1,2,4,6 Acromegalic skin confers a viscous, humid and intumescent aspect to the touch.
Hyperhydrosis is considered to be the most reliable clinical sign of disease activity. Hyperpigmentation occurs in roughly 40% of cases and almost always in photoexposed areas. It is probably due to the associated increase of melanotrophic hormone.
Acanthosis negricans occurs in 10% of cases. Hypertrophic scarring is common. In cases when disease course is longer, cutis verticis gyrata may be observed. Acrocordon is frequent (30% of cases), and may be an indicator of polyp and adenocarcinoma of the colon. Acromegaly also causes the Sign of Leser-Trelat (i.e., the eruption of multiple lesions of seborrheic keratosis).1,2,6-9 Some cutaneous manifestations, such as hirsutism and sebaceous hypersecretion, may result from the free testosterone carrier protein. Found at reduced levels in acromegaly, the protein therefore allows a higher proportion of testosterone in a free state.3,5 An interesting alteration not described in the research literature but observed in the authors' own clinical practice, is an elevation of the dorsal-to-sole transition of the foot. (Figures 1, 2 and 3).
The general manifestations include neurological symptoms (headache, diplopia, bitemporal hemianopsia, carpal tunnel syndrome), osteoarthritis, visceromegalies, cardiomegaly, arterial hypertension, hypercalciuria and hoarseness (cartilaginous proliferation of the larynx). Hyperprolactinemia occurs in 20 to 30% of cases, and determines galactorrhea, impotency and/or diminution of the libido and menstrual irregularities. Due to excess growth hormones, peripheral resistance to insuline develops in close to 50% of cases. However, clinically manifested diabetes mellitus occurs in only 10% of these patients.1,2,6,7
The clinical diagnosis is confirmed by the growth hormone dose or by somatomedine-C for radioimmune assays, which are notably high in patients with acromegaly. Growth hormones higher than 2 ng/ml (for men) or 5 ng/ml (for women) is compatible with the laboratory diagnosis of acromegaly. The suppression test with oral glycose or the glycemic curve became useful when the growth hormone level was not characteristically high. This is due to the fact that contrary to what normally happens in persons to whom glycose is administered, growth hormone levels remain high in acromegaly. The radiography, computerized tomography and magnetic resonance of the sella turcica are used to evidence hypophysis adenoma and its extension.6,7 Meanwhile, two rare syndromes must be considered different from acromegaly: Rosenthal-Kloepfer syndrome and Soto's syndrome, both developing with acromegaloid characteristics. In the former, cutaneous corns in the lateral half of the upper-orbital margin, cutis vertice gyrata and opacity of the cornea are all characteristic. There are no alterations of the endocrine or of the sella turcica. In Soto's syndrome mental retardation is encountered, as are tall stature and weight increase.10
Treatment consists of microsurgery of the hypophysis via transesphenoidal, radiotherapy and octreotide. Surgical management is generally successful. Octreotide is a potent growth hormone release inhibitor, administered subcutaneously in 50 to 200 microgram doses three times daily.6,7 11
In its evolution, medicine has become specialized, but the holistic vision is still indispensable for any medical specialty. In this sense, the authors sought to revise the main and attendant clinical elements of acromegaly endocrine disorder coursing with systemic clinical manifestations that include the skin. The disorder shows slow and gradual symptomatological progression, but with premature cutaneous alterations. The main clinical expressions of this affliction are intumescence of the acral cartilegenous-bone tissue. An interesting observation observed in the authors' clinical practice is the elevation of the dorsal-to-sole transition of the foot. The dermatologist may indeed be the medical professional to first establish this syndrome or suspect it, potentially leading the patient to early treatment.
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Received on September 04, 2001.
Approved by the Consultive Council and accepted for publication on August 07, 2002.
* Work done at Prof. Dr. Luiz Henrique C. Paschoal, Dermatology Service, Fundação ABC Medical Faculty.