Cattedra di Endocrinologia Università di Catania I-95123 Catania, Italy
A 56-yr-old man was admitted to our department because of
recurrent and severe hypoglycemia. Ten years previously the patient had
undergone surgery for an intraabdominal hemangiopericytoma, a
mesenchymal tumor. An ileocolectomy with colostomy was performed about
twenty months later because of local recurrence of the tumor. He was
apparently well thereafter until 2 years before the admission to our
department, when he was treated with chemotherapy and radiotherapy
because of a small mass in the pelvis evidenced at a computed
tomography scan. Two months before admission to our department, he was
brought to the emergency room in a state of unconsciousness and with a
plasma glucose level of 20 mg/dL (1.1 mM). He was given
20% dextrose iv, and he promptly recovered. The hypoglycemic episodes
recurred and became more frequent. Upon admission to our department the
patient was first treated with 50% dextrose infusion through a
subclavian vein. Nevertheless episodes of hypoglycemia persisted,
especially at night, when fasting was longer than 45 hr. Increased
meal frequency with complex carbohydrates administration plus
continuous dextrose infusion were no longer able to control
hypoglycemia. The patient had normal-to-low plasma insulin levels and
very high levels of insulin-like growth factor (IGF)-II, especially in
the isoform 1017 kDa, around 80% of total measured IGF-II (Fig. 1and Table 1
). The diagnosis of nonislet cell tumor hypoglycemia (NICTH) was
proposed. Evaluation of liver showed metastatic lesions, but because of
the size, a palliative surgical attempt was not advised. Therapy with
both prednisone (15 mg/day per os) and, after informed consent,
biosynthetic GH (2 U/day sc) at bedtime was soon started. Dextrose
infusion was gradually reduced and eventually suspended 4 days after
beginning continued hormone treatment. No further episode of
hypoglycemia occurred in the following 3 days, and he was discharged
from the hospital in apparent good condition with instructions for
blood glucose self monitoring and glucagon use in the case of severe
hypoglycemia.
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It has been reported that mesenchymal tumors may produce and release an excessive amount of IGF-II as well as the isoform called big IGF-II (1). This high molecular weight IGF-II is considered the causative agent of NICTH because of its insulin-like effect, exherted primarily by stimulating glucose uptake at peripheral tissue level (2). In addition, the increased serum IGF-II inhibits both GH and insulin secretion and, as a consequence, lowers the plasma concentration of insulin and GH-dependent IGF binding proteins (mainly IGFBP-3). This in turn increases the unbound IGF-II fraction and worsens its hypoglycemic effect (3).
When surgical removal or radiotherapy is not advised, many other
strategies may ameliorate a patients severe hypoglycemia, including
corticosteroid administration (which, in addition to its
antihypoglycemic action, may also suppress IGF-II production by the
tumor) (4) and subcutaneous glucagon infusion (5). GH treatment has
also been tried in such patients (6, 7), with the postulated mechanism
of reducing IGF-II availability to tissues by increasing IGFBP-3 levels
and the acid labile subunit (ALS) that will form the "ternary
complex" containing bound (biologically nonactive) IGF-II. In vitro
GH does not appear to have any significant mitogenic effect (8, 9).
Increased cancer prevalence in acromegaly is probably a consequence of
elevated IGF-1 levels (10). In our patient, however, plasma IGF-1
remained low during hGH treatment at the doses used (Table 1).
In this very severe case of NICTH the combined treatment with prednisone and GH proved effective in ameliorating the hypoglycemic syndrome without side-effects. It can therefore be proposed as a cost-effective palliative treatment in these patients.
Footnotes
Address correspondence to: Dr. Damiano Gullo, Divisione Endocrinologia, Ospedale Garibaldi, Piazza S. M. Gesù, I-95123 Catania, Italy.
Received December 1, 1998.
References
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