Correspondence

Pituitary Carcinoma as a Cause of Acromegaly

N Engl J Med 2001; 345:1645-1646November 29, 2001

Article

To the Editor:

Only nine cases of acromegaly caused by pituitary carcinoma have been reported.1 We describe a 47-year-old woman who presented in July 1996 with the features of acromegaly and an elevated mean serum growth hormone level of 58.4 mU per liter. Magnetic resonance imaging demonstrated an extensive homogeneous pituitary mass compressing the optic chiasm, with extension to the suprasellar region and the right middle cranial fossa. Debulking was attempted transcranially, and histologic examination confirmed a pituitary adenoma that stained for growth hormone. The serum insulin-like growth factor I (IGF-I) level remained elevated at 158 nmol per liter (age- and sex-specific reference range, 13 to 64), but the mean serum growth hormone level decreased (29.7 mU per liter). The serum growth hormone level was not suppressed during an oral glucose-tolerance test, and administration of subcutaneous octreotide was begun at 100 μg three times a day and increased to 200 μg three times a day. In March 1997, the patient received 50 Gy of conventional three-field radiotherapy. Six months later, the IGF-I level decreased to 89.5 nmol per liter.

In September 1998, the pituitary lesion remained stable on consecutive magnetic resonance imaging scans, but the IGF-I level had increased (to 111.5 nmol per liter), resulting in a change in therapy to 30 mg of intramuscular lanreotide every 14 days. The patient noticed a lump on the right side of her neck, and a lymph node removed for histologic examination in February 1999 revealed a metastasis that was cytomorphologically identical to the pituitary adenoma and also immunostained for growth hormone (Figure 1Figure 1Positive Immunostaining for Growth Hormone in the Lymph-Node Mass from the Right Side of the Patient's Neck.). A dramatic decrease in the IGF-I level (60 nmol per liter) and the mean serum growth hormone level (6.7 mU per liter) followed. Lanreotide was discontinued for six weeks, and both octreotide and metaiodobenzylguanidine scans were negative. We therefore conducted follow-up using clinical examination and biochemical markers. In February 2000, the IGF-I level (122 nmol per liter) and the serum growth hormone level (20.3 mU per liter) increased, so lanreotide therapy was recommenced.

The patient experienced increased sweating. Magnetic resonance imaging of the neck confirmed that the lymph nodes were increasing in size (Figure 2Figure 2Magnetic Resonance Imaging of the Lymph-Node Mass in the Right Side of the Patient's Neck.). A neck dissection was performed in June 2000, and histologic examination showed that 10 of 21 lymph nodes contained metastatic pituitary carcinoma, with positive immunostaining for growth hormone. Cell cultures confirmed production of growth hormone. Six months after surgery, the serum growth hormone level decreased to 3.1 mU per liter and the IGF-I level decreased to 62.7 nmol per liter, with an improvement in symptoms.

One other case of acromegaly caused by pituitary carcinoma metastasizing outside the central nervous system has been reported.2 Both patients had nodal metastases in the neck after cranial radiation, which raises the issue of malignant transformation of a benign pituitary adenoma. In contrast to the first patient, our patient had a negative octreotide scan. Surgery was the only option, but because of the insidious nature of the tumor, which behaves similarly to other neuroendocrine tumors, the prognosis remains indeterminate and future treatment options are limited. Pituitary carcinoma should be considered when a pituitary mass remains stable but biochemical markers remain abnormal. A careful physical examination and octreotide scintigraphy should be the first steps before histologic confirmation is sought.

Carel W. le Roux, M.R.C.P.
Abeda Mulla, B.Sc.
Karim Meeran, F.R.C.P.
Imperial College School of Medicine, London W6 8RF, United Kingdom
c.leroux@ic.ac.uk

2 References

1. 1

   Dayan C, Guilding T, Hearing S, et al. Biochemical cure of recurrent acromegaly by resection of cervical spine canal metastases. Clin Endocrinol (Oxf) 1996;44:597-602
   CrossRef | Web of Science | Medline

2. 2

   Greenman Y, Woolf P, Coniglio J, et al. Remission of acromegaly caused by pituitary carcinoma after surgical excision of growth hormone-secreting metastasis detected by 111-indium pentetreotide scan. J Clin Endocrinol Metab 1996;81:1628-1633
   CrossRef | Web of Science | Medline

Citing Articles (2)

Citing Articles

1. 1

   Brian T. Ragel, William T. Couldwell. (2004) Pituitary carcinoma: a review of the literature. Neurosurgical FOCUS 16:4, 1-9
   CrossRef

2. 2

   Abeda Mulla, Helen C. Christian, Egle Solito, Nigel Mendoza, John F. Morris, Julia C. Buckingham. (2004) Expression, subcellular localization and phosphorylation status of annexins 1 and 5 in human pituitary adenomas and a growth hormone-secreting carcinoma. Clinical Endocrinology 60:1, 107-119
   CrossRef