Somatostatin Analog and Estrogen Treatment in a Tall Girl

Clin Pediatr Endocrinol 1995; 4 (2): 163-167 Copyright (C) 1995 by The Japanese Society for Pediatric Endocrinology Somatostatin Analog and Estrogen Treatment in a Tall Girl Toshiaki Tanaka, Mari Satoh, Masayuki Kokaji, Ayako Tanae, Itsuro Hibi Department of Endocrinology and Metabolism, National Children's Medical Research Center, (TT: MS), Division of Endocrinology and Metabolism, National Children's Hospital, (TT, MK, AT, IH), Tokyo, Japan Abstract A girl aged 10 years and 7months who was 168.9 cm tall was diagnosed as having familial tall stature and was treated with a combination of octreotide acetate (50 Đg. sc injection three times daily) and Kaufmann therapy (Premarin 2.5 mg/day for 26 days a month with Provera 10 mg for the last 7 days with Premarin, cyclically) for 25 months to reduce final height. Serum insulin-like growth factor I (IGF-I) and the urinary growth hormone (GH) level decreased and serum gonadotropins were completely suppressed during the treatment. After discontinuation of the treatment, serum IGF-I, urinary GH, and gonadotropins returned to the pubertal level. Her height velocity decreased and bone age advanced from 11.4 years to 14 years during the 25-month treatment. When the treatment was discontinued at the chronological age of 12 years and 11 months, her bone age was 14 years and her height was 176.4 cm. She has almost stopped growing at 13 years and 11 months, and has reached a final height of 177.6 cm. Since the patient grew only 7.9 cm during puberty, it can be concluded that the combination treatment was very effective in reduction of final height. Key words: tall girl, familial tall stature, estrogen therapy, octreotide acetate Introduction Tall stature is generally considered an asset in our society, and most tall children accept their height without difficulty. However, tall girls sometimes have psychosocial problems. Tall girls whose final height is predicted to exceed 180 cm feel especially uncomfortable about their social lives, and this also troubles their parents. High-dose estrogen treatment is generally used to reduce the final height of especially tall girls (1-4), but such treatment for tall girls is still not well established. In this report, we describe how an extremely tall girl was treated with a combination of somatostatin analog and high-dose estrogen. Case Received: September 1, 1995 Accepted: October 4, 1995 Correspondence: Dr. Toshiaki Tanaka, Department of Endocrinology and Metabolism, National Children's Medical Research Center, 3-35-31, Taishido, Setagaya-ku, Tokyo 154 Japan A girl aged 10 years and 7 months was examined for her tall stature. She was 168.9 cm tall (+5 standard deviation (SD)) and weighed 52.45 kg (+3 SD). She had many tall relatives, 163

Vol. 4/No. 2 Tanaka et al. including her parents, as shown in Fig. 1. She was born after a 41-week gestation without any complication. She was 3,800 g and 54 cm at birth. She had operations for an ear bone anomaly twice at 9 and 10 years. She had suffered from headaches since the age of 9 years and was treated with an anticonvulsant following a diagnosis of epileptic headache based on electroencephalogram (EEG) abnormalities. At 10 years and 7 months, her pubertal development was Tanner stage 2 with only breast budding and her bone age was 11.7 years. Skull X-rays and CT scans showed no abnormal findings. The urinary amino acid analysis was also normal. Her EEG showed spike and wave bursts. The endocrinological findings were serum IGF-I 390 ng/ml, urinary GH 32.2 pg/mgcr, thyroxine (T4) 73 Đg/dl, 3,5,3'-triiodothyronine (T3) 1.5 ng/ml, and thyrotropin (TSH) 0.5 U/mL. Serum GH increased from 4.8 ng/mlĐ to 71.7 ng/ml by the glucagon-propranolol stimulation test (Fig. 2). The serum GH response was 19.7 ng/ml to TSH-releasing hormone (TRH)(Fig. 2) and 21.9 ng/ml to bromocriptine. Serum GH was suppressed from a basal level of Fig. 2 Serum GH responses to stimulation tests 5.6 ng/ml to 2.9 ng/ml by the oral glucose tolerance test, but rebounded to 19 ng/ml at 90 minutes (Fig. 2). The glucose pattern was normal. Spontaneous GH secretion was measured every 20 minutes and the mean GH level for 24 hours was 11.6 ng/ml. The luteinizing hormone-releasing hormone (LH-RH) test showed pubertal gonadotropin responses (peak luteinizing hormone (LH) 8.8 miu/ml, peak follicle stimulating hormone (FSH) 6.7 miu/ml). Bone age was estimated by one observer using the TW2 RUS method standardized for Japanese. Results At 10 years and 9 months of age and a height of 170 cm, the patient started to receive Kaufmann therapy (Premarin 2.5 mg/day for 26 days a month with Provera 10 mg for the last 7 days with Premarin, cyclically) and somatostatin analog treatment (50 Đg octreotide acetate s.c. injection three times a day). Combined treatment was continued for 25 months Fig. 1 Height of family members. and discontinued at 12 years 11 months. 164

December 1995 Somatostatin & Estrogen Treatment in a Tall Girl Spontaneous GH secretion was measured every hour with somatostatin analog treatment (50 Đg octreotide acetate s.c. injection three times a day) and compared with the data before treatment (Fig. 3). The mean GH level for 24 hours decreased to 5.8 ng/ml with octreotide acetate treatment. The serum IGF-I level decreased to the range 180 to 260 ng/ml during treatment and returned to the pretreatment level after discontinuation of the treatment (Fig. 4). The urinary GH level also decreased to the range 11.5 to 19.5 pg/ml during treatment and returned to the pretreatment level after treatment (Fig. 4). The serum estradiol level was extremely elevated and serum LH and FSH completely suppressed during treatment. Both values returned to the pubertal level after treatment (Fig. 5). Bone age advanced from 11.4 years at the start of treatment (chronological age (CA); 10 years and 9 months) to 12 years at the CA of 11 Fig. 5 Change in serum LH, FSH and estradiol octreotide and Kaufmann treatment. Fig. 3 Spontaneous GH secretion with or without octreotide treatment. Arrows show octreotide administration. Fig. 4 Change in serum IGF-I and urinary GH during octreotide and Kaufmann treatment. Fig. 6 Growth chart of the patient. 165

Vol. 4/No. 2 Tanaka et al. years and 3 months, to 13.3 years at the CA of 11 years and 11 months and to 14 years at the CA of 12 years and 11 months (Fig. 6). Growth velocity, which was 8.5 cm/year before treatment, decreased to 4.5 cm/year in the first year and 2.1 cm/year in the second year. Pubertal stage developed to breast development stage 3, pubic hair stage 2 at 2 months of treatment, to breast development stage 4 at 3 months of treatment, and to full pubertal maturation (stage 5) at 9 months of treatment. Treatment was discontinued at the CA of 12 years and 11 months, when the patient's bone age was 14 years and her height was 176.4 cm. Spontaneous regular menstruation started 5 months after discontinuation of the treatment at 13 years and 4 months. At 13 years and 11 months, her height was 177.6 cm. Discussion The majority of healthy tall children have familial tall stature. The presented case also has a family history of tall stature. The patient was nevertheless evaluated to exclude a diagnosis of pituitary gigantism. Her spontaneous GH secretion was rather high and the GH response to glucagon-propranolol was also high. However, IGF-I level was within the normal range, and her GH level was suppressed marginally, tested by the oral glucose tolerance test. Paradoxical GH response to TRH cannot be diagnostic for pituitary adenoma, since tall children can be responsive to the TRH test (5). Tall children have been reported to secrete more GH than normal children (5, 6). Although her GH secretory capacity was rather high, we diagnosed her as not having pituitary gigantism because of negative CT findings. treatment Estrogen therapy is recommended for the of tall girls (1-4). The effect of estrogen on epiphyseal closure was revealed to be essential by recent reports of a case with estrogen receptor defect (7) and a case with aromatase deficiency (8), who had tall stature without epiphyseal fusion after a chronological age of 20 years. Octreotide acetate therapy is reported to be effective in acromegaly (9, 10). Since octreotide acetate was known to reduce GH secretion in this patient, a combination of high-dose estrogen with progesterone to induce menstruation and octreotide therapy was employed. Octreotide effectively reduced the urinary GH level and serum IGF-I. High-dose estrogen completely suppressed gonadotropin levels and advanced her bone age. Her growth rate was also decreased and bone age reached 14 years during treatment. A patient's growth potential at bone age 14 years is minimum. This patient has almost stopped growing at 13 years and 11 months, and reached her final height of 177.6 cm. Her predicted adult height was 184 cm using the Bailey-Penneau method adjusted for Japanese girls and it was also 184 cm by the projected height using height SD score for bone age at the start of the treatment. Normal girls usually grow from 20 to 25 cm during puberty, and tall girls are expected to grow even more than normal girls. Since the patient grew only 7.9 cm during puberty, it can be concluded that this combination therapy was very effective in reduction of final height. References 1. Svan H, Ritzen EM, Hall K, Johansson L. Estrogen treatment of tall girls: dose depen- 166

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