Pregnancy is a rare event in patients with acromegaly, probably because of the frequently associated hyperprolactinemia and altered gonadotropin secretion. With the advent of effective and selective therapeutic management of these patients, more women with acromegaly are becoming pregnant. Until recently, reports of the outcome of pregnancy in women with acromegaly were scant. We report here the case of a woman with acromegaly who became pregnant shortly after treatment with octreotide long-acting release (LAR) and who had, after cessation of the medication, an unusual remission of her disease for the duration of the pregnancy. This report reviews the literature on pregnancy in patients with acromegaly treated with somatostatin analogues.
The 33-year-old patient, mother of two children (aged 5 and 3 years) sought treatment in 1999 with a 2-year history of post-partum amenorrhea-galactorrhea and enlargement of hands and feet. She was investigated for suspected acromegaly. Mean basal serum GH was 8 μg/L and was not suppressed by an oral glucose test (OGTT). Insulin-like growth factor (IGF-I) was 856 μg/L (normal levels being 122–400 μg/L); prolactin (PRL) was 65 μg/L (normal values 4–18 μg/L). A pituitary magnetic resonance image (MRI) demonstrated a microadenoma 5 mm in diameter. The patient underwent a selective adenomectomy by transsphenoidal surgery in February of 2000. Two months after surgery, acromegaly was still clinically evident with amenorrhea and hyperhidrosis. PRL was 39 μg/L, IGF-I 748 μg/L and nadir GH value during OGTT was 3 μg/L. Treatment with octreotide LAR, 20 mg every 4 weeks, was begun in May 2000. Six weeks after the first injection, menses resumed. After the fourth injection, the patient became pregnant. Octreotide was stopped and visual fields, glucose tolerance and IGF-I levels were assessed every 3 months. Throughout pregnancy, the patient experienced clinical well-being, regression of skin thickening and hypertrichosis, and significant reduction of enlargement of extremities. Visual field examinations and glucose tolerance were normal. Serum IGF-I concentrations were 250 μg/L at 3 months, 229 μg/L at 6 months, and 353 μg/L before delivery (Fig. 1). PRL concentrations were 36 μg/L at 6 months and 35 μg/L before delivery. Pregnancy was uncomplicated and the patient delivered vaginally a normal, full-term infant in April of 2001. The baby weighed 3.8 kg. The infant was breast-fed for 3 months and had normal postnatal development. The maternal serum IGF-I levels increased rapidly after delivery and reached 398 μg/L in May, 477 μg/L in June and 666 μg/L in August (Fig. 1). On that occasion, PRL was 55 μg/L and nadir GH during OGTT was 1.3 μg/L. Octreotide LAR was resumed.
Somatostatin analogs are an established treatment option in active acromegaly, especially if there is no remission following surgery. Their use in women with acromegaly who become pregnant has been reported only a few times. To our knowledge, 14 women with acromegaly have received octreotide, octreotide LAR or Lanreotide before or during their pregnancy [1–12] (Table 1). With the exception of three cases, the somatostatin analog was stopped during early pregnancy. Theoretically, the benefit of treatment throughout pregnancy is in controlling active acromegaly and improving glucose tolerance thereby reducing the risk for increased fetal birth weight. Pregnant women with acromegaly are at increased risk for impaired glucose tolerance and diabetes mellitus . The birth weights of the reported newborns are greater than the 97th percentile . However, the possible risk for somatostatin analog therapy throughout pregnancy would be fetal growth retardation caused by placental passage of the drug.
In our patient who stopped octreotide LAR with the diagnosis of pregnancy, glucose tolerance was normal throughout pregnancy and the weight of her newborn was between the 50th and the 75th percentile, lower than that of her previous pregnancy. Although the drug was discontinued after diagnosis of pregnancy, the embryo had been exposed to octreotide LAR during the first weeks of gestation. The newborn showed no malformations and had normal postnatal development. Although there were no malformations in the 15 cases in the literature (Table 1), the number is too small to be certain that octreotide is not teratogenic.
In normal pregnancy and in women with active acromegaly, IGF-I levels rise significantly during the third trimester as a result of increased placental GH secretion . In only one woman with acromegaly was there a decreased IGF-I level throughout pregnancy because of treatment with radiotherapy and octreotide before pregnancy . In our case, although octreotide LAR was stopped during early pregnancy, plasma IGF-I concentrations remained within the normal range of nonpregnant women even during the third trimester. Three months after delivery, however, IGF-I increased rapidly to the elevated pretreatment levels. The clinical parameters of acromegaly improved during the course of pregnancy. One possible mechanism to explain this is an enhanced sensitivity to octreotide LAR with prolonged effect during pregnancy. Alternatively, a tumor infarction may have occurred following the stimulatory effect of peripheral hormone surges during pregnancy. This seems unlikely in view of the absence of clinical signs of infarction and recurrence of the disease following delivery. Most likely, in our opinion, is that the increased serum estrogen levels during pregnancy caused a reduction in serum IGF-I levels, as suggested by studies of estrogen therapy in nonpregnant acromegalics [14,15].
Our case of uneventful pregnancy in acromegaly treated with long-acting octreotide LAR, together with the previous reported cases, suggests that octreotide treatment during early pregnancy is feasible. Our case also illustrates an unusual pattern of persistently normal IGF-I levels during the pregnancy and when octreotide treatment was discontinued. The dynamics of IGF-I throughout pregnancy in acromegalics following octreotide LAR treatment should be studied further.
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