Mosaic Effects of Growth Hormone on Fibrous Dysplasia of Bone

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cured patients (12.2% [95% CI, 10.2 to 14.2] vs. Bhaskar Saha, Ph.D. 1.2% [95% CI, 0.7 to 1.8]) Fig. 1C and 1D). National Centre for Cell Science Among the 5 patients who were positive for para- Pune, India sites at day 3, the isolates from 4 patients had Amiya K. Hati, M.B., B.S., Ph.D. School of Tropical Medicine the kelch13 G625R mutation, and the isolate Calcutta Kolkata, India from the other patient had the R539T mutation. In accordance with the WHO criteria, these Somenath Roy, Ph.D. Vidyasagar University 5 isolates were thus identified as being arte- Midnapore, India misinin-resistant. roysomenath1954@​­yahoo​.­in Supported by a grant from the Council for Scientific and IndusIn this study, we identified G625R as a potenResearch, Government of India (09/599 [0055] 2K1-EMR-1, tial novel mutation that, along with R539T, is as- trial to Dr. Das). sociated with artemisinin resistance. Other mutaDisclosure forms provided by the authors are available with tions in kelch13 have previously been reported,4,5 the full text of this letter at NEJM.org. but how this newly identified mutation affects 1. Yeung S, Pongtavornpinyo W, Hastings IM, Mills AJ, White artemisinin resistance and the outcome of in- NJ. Antimalarial drug resistance, artemisinin-based combinafection remains to be elucidated. Although tion therapy, and the contribution of modeling to elucidating choices. Am J Trop Med Hyg 2004;​71:​Suppl:​179-86. artemether–lumefantrine is recommended in policy 2. Guidelines for diagnosis and treatment of malaria in India. northeastern India, artesunate–sulfadoxine–pyri- New Delhi, India:​National Institute of Malaria Research, 2009 methamine is still the first-line medicine in the (http://nvbdcp​.gov​.in/​Doc/​Guidelines_for_Diagnosis___Treatment​ rest of India.2 Our findings with regard to early .pdf). 3. Flegg JA, Guerin PJ, White NJ, Stepniewska K. Standardizing treatment failure related to artemisinin resistance the measurement of parasite clearance in falciparum malaria: and late treatment failure due to partner-drug the parasite clearance estimator. Malar J 2011;​10:​339. 4. Global Malaria Programme. Artemisinin and artemisininresistance emphasize the need for increased based combination therapy resistance: status report. Geneva: surveillance of drug resistance in order to man- World Health Organization, October 2016 (http://apps​.who​.int/​ iris/​bitstream/​10665/​250294/​1/​WHO​-­HTM​-­GMP​-­2016​.11​-­eng​.pdf). age the spread of resistant parasites. 5. Mishra N, Bharti RS, Mallick P, et al. Emerging polymor-

Sabyasachi Das, Ph.D.

phisms in falciparum Kelch 13 gene in northeastern region of India. Malar J 2016;​15:​583.

Vidyasagar University Midnapore, India

DOI: 10.1056/NEJMc1713777

Mosaic Effects of Growth Hormone on Fibrous Dysplasia of Bone To the Editor: Fibrous dysplasia and the McCune– Albright syndrome constitute a rare mosaic disorder caused by somatic activating mutations of Gαs (the G-protein subunit αs). Characteristic manifestations, including café-au-lait skin lesions, fibrous dysplasia of bone, and hyperfunctioning endocrinopathies, occur with varying severity, depending on the embryonic stage at which the mutation occurred. Mutations early in embryogenesis result in multiple affected tissues, whereas later mutations result in more limited manifestations.1 Growth hormone excess is an endocrinopathy that is associated with the McCune–Albright syndrome. In one study involving 58 patients with the McCune–Albright syndrome,2 21% of the patients did not have suppression of growth hormone on an oral glucose-tolerance test. Of these 12 patients, 4 had vision and hearing deficits that were related to cranial expansion.2 Early diagnosis and treatment of growth hormone ex1964

cess have significantly decreased the incidence of optic neuropathy.3 Typical features of growth hormone excess include coarsened facies, cardiovascular disease, and overgrowth of the hands and feet. A classic radiographic finding is distal tufting of the phalanges.4 In patients with fibrous dysplasia and the McCune–Albright syndrome, these skeletal features of growth hormone excess are exaggerated, as we discuss in the following case. A 21-year-old man had received a diagnosis of fibrous dysplasia and the McCune–Albright syndrome at 3 years of age, after a bone fracture. Throughout childhood, he had progressive skull expansion and asymmetric expansion of the fingers. His linear growth was unremarkable, and he reached a predicted midparental height of 172 cm. Physical examination revealed prominent finger pulp and widening of the distal phalangeal tips on the left hand, as compared

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Correspondence

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Figure 1. Patient with Fibrous Dysplasia and the McCune–Albright Syndrome. Shown are photographs of the patient’s left hand, which was affected by fibrous dysplasia in the context of growth hormone excess, as compared with his unaffected right hand. The left hand shows prominent finger pulp and widening of the left distal phalangeal tips (Panel A), as compared with the right hand (Panel B). Radiographs show the distal bone overgrowth of the affected left hand (Panel C), as compared with the subtle tufting of the normal right hand (Panel D). Magnetic resonance imaging of the head (Panel E) revealed enlargement of the pituitary gland (arrow) and expansion of the cranium and skull base, which were affected with fibrous dysplasia (asterisks).

with the right hand (Fig. 1A and 1B). A bone scan revealed mosaic involvement, with fibrous dysplasia affecting his arm and leg on the left side and his skull. Baseline serum levels of growth hormone and insulin-like growth factor 1 were elevated at 3.82 ng per milliliter (normal value,