Correspondence
Acromegaly
N Engl J Med 2007; 356:1274-1276March 22, 2007
- Article
To the Editor:
In Melmed's otherwise excellent review of acromegaly (Dec. 14 issue),1 the clinical myth that headache is due to a local tumor effect is perpetuated in Table 1. It has been established in a prospective study that the size of a pituitary tumor does not determine the headache presentation.2 Moreover, the phenotype of headache presentations is wide, including migraine and the trigeminal autonomic cephalalgias, particularly cluster headache.3 An important clinical lesson in this context is the overrepresentation of cluster-headache–like presentations in patients with acromegaly and thus the higher yield in searching for pituitary-tumor–related disease when one sees atypical headache presentations.
3 ReferencesPeter J. Goadsby, M.D., Ph.D.
University of California at San Francisco, San Francisco, CA 94143-0114
goadsbyp@neurology.ucsf. edu 1
Melmed S . Acromegaly. N Engl J Med 2006;355:2558-2573
Full Text | Web of Science | Medline2
Levy MJ ,Jager HR ,Powell MP ,Matharu MS ,Meeran K ,Goadsby PJ . Pituitary volume and headache: size is not everything. Arch Neurol 2004;61:721-725
CrossRef | Web of Science | Medline3
Levy MJ ,Matharu MS ,Meeran K ,Powell M ,Goadsby PJ . The clinical characteristics of headache in patients with pituitary tumours. Brain 2005;128:1921-1930
CrossRef | Web of Science | Medline
To the Editor:
Melmed does not emphasize the unique and highly characteristic visual abnormalities in patients with acromegaly. Nearly 20% of patients with this condition have some sort of visual-field abnormality.1 Most of these defects occur because of compression of the optic chiasm by the enlarged pituitary.2 Bilateral visual defects are more common than unilateral defects, with bitemporal hemianopsia and superior bitemporal quadranopsia being the most commonly detected defects.3 Other, less common defects include unilateral temporal hemianopsia, superotemporal quadranopsia, and inferotemporal quadranopsia. The earliest visual-field defect is usually in the superior temporal quadrant. In general, patients with visual-field defects tend to have higher levels of growth hormone and are usually younger than patients without such defects.4 Also, larger tumors are associated with more suprasellar extension and thus more extensive visual defects. Remarkably, these visual defects improve significantly after surgical treatment of acromegaly. A success rate as high as 70% was reported in one study.1 Physicians should be aware of these visual defects, since they are unique and have a high diagnostic value.
4 ReferencesShailendra Kapoor, M.D.
University of Illinois at Chicago, Chicago, IL 60612
skapoor5@uic.edu 1
Rivoal O ,Brezin AP ,Feldman-Billard S ,Luton JP . Goldmann perimetry in acromegaly: a survey of 307 cases from 1951 through 1996. Ophthalmology 2000;107:991-997
CrossRef | Web of Science | Medline2
Foroozan R . Chiasmal syndromes. Curr Opin Ophthalmol 2003;14:325-331
CrossRef | Medline3
Centurion SA ,Schwartz RA . Cutaneous signs of acromegaly. Int J Dermatol 2002;41:631-634
CrossRef | Web of Science | Medline4
Hennessey JV ,Jackson IM . Clinical features and differential diagnosis of pituitary tumours with emphasis on acromegaly. Baillieres Clin Endocrinol Metab 1995;9:271-314
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To the Editor:
Melmed points out that cardiovascular disease (e.g., hypertension) is present in 60% of affected patients at the time of diagnosis and that progression (e.g., to myocardial hypertrophy and heart failure) occurs with time. However, he does not mention that the hypertension is low-renin hypervolemic hypertension, which is associated with inhibition of sodium–potassium ATPase and the sodium–potassium pump at the cell and tissue levels in the cardiovascular system.1 Furthermore, plasma contains an inhibitor of the sodium–potassium pump, an endogenous digitalis-like factor (DLF). Deray et al.2 found elevated levels of plasma DLF in patients with acromegaly. They also showed that the activity of DLF in plasma correlates inversely with plasma renin activity and directly with plasma volume and arterial pressure. Now it appears that the inhibitors seen in volume-expanded states are steroids released from the adrenal gland and are members of the cardenolide family (e.g., ouabain) and the bufadienolide family (e.g., marinobufogenin).3 This finding presents new possibilities for future therapy, such as the development of antibodies to these agents and competitive inhibitors of their binding to sodium–potassium ATPase.
3 ReferencesFrancis J. Haddy, M.D., Ph.D.
Mayo Clinic College of Medicine, Rochester, MN 559051
Haddy FJ . Endogenous digitalis-like factor or factors. N Engl J Med 1987;316:621-623
Full Text | Web of Science | Medline2
Deray G ,Rieu M ,Devynch MA , et al. Evidence of an endogenous digitalis-like factor in the plasma of patients with acromegaly. N Engl J Med 1987;316:575-580
Full Text | Web of Science | Medline3
Bagrov AY ,Fedorova OV . Cardenolide and bufadienolide ligands of the sodium pump: how they work together in NaCl sensitive hypertension. Front Biosci 2005;10:2250-2256
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Author/Editor Response
Because of space limitations, my review article was geared toward relevant recent advances in understanding the pathogenesis, clinical treatments, and outcomes of acromegaly. The three correspondents point to important physical signs of acromegaly (including headache, visual disturbances, and hypertension), all of which are relatively commonly encountered in the general population. In a comprehensive review of 310 patients with acromegaly, headache and visual defects were reported as presenting features in 8% and 3% of patients, respectively.1
Headache that is associated with acromegaly may be multifactorial, with no known definitive cause. In Table 1 of my article, clinical features of acromegaly were classified according to system, not cause. Headache was included as a feature of the disease. In fact, treatment with somatostatin analogues may ameliorate headache, independently of tumor size.2
Although the article does, in fact, list visual-field defects as a clinical feature associated with acromegaly, recent comprehensive surveys of patients with the condition have deemphasized the importance of these signs, with reported prevalence rates ranging from 0 to 15%.3,4 This finding probably reflects both earlier presentation of patients and improved diagnostic awareness. Furthermore, since invasive growth hormone–secreting macroadenomas commonly grow laterally toward the cavernous sinus, the chiasm is usually spared from impingement in these patients.
Hypertension is mentioned in the article as an important determinant of the rates of coexisting illness and death in patients with acromegaly. The pathogenesis of hypertension in acromegaly remains enigmatic and is probably multifactorial. Reduced secretion of atrial natriuretic peptide, peripheral insulin resistance, sodium retention, volume expansion, disrupted catecholamine rhythms, and structural blood-vessel narrowing have all been proposed as pathogenetic factors,5 in addition to those mentioned in the older study cited by Haddy. None of these mechanisms have been definitely proved, and treatment of hypertension in patients with acromegaly should follow standard guidelines.
5 ReferencesShlomo Melmed, M.D.
Cedars-Sinai Medical Center, Los Angeles, CA 90048
melmed@cshs.org 1
Molitch ME . Clinical manifestations of acromegaly. Endocrinol Metab Clin North Am 1992;21:597-614
Web of Science | Medline2
Musolino NR ,Marino Junior R ,Bronstein MD . Headache in acromegaly: dramatic improvement with the somatostatin analogue SMS 201-995. Clin J Pain 1990;6:243-245
CrossRef | Web of Science | Medline3
Ezzat S ,Forster MJ ,Berchtold P ,Redelmeier DA ,Boerlin V ,Harris AG . Acromegaly: clinical and biochemical features in 500 patients. Medicine (Baltimore) 1994;73:233-240
Web of Science | Medline4
Drange MR ,Fram NR ,Herman-Bonert V ,Melmed S . Pituitary Tumor Registry: a novel clinical resource. J Clin Endocrinol Metab 2000;85:168-174
CrossRef | Web of Science | Medline5
Colao A ,Ferone D ,Marzullo P ,Lombardi G . Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr Rev 2004;25:102-152
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