Diagnosis and Treatment > Medication

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Guadalupe Vargas Endocrinology Service and Experimental Endocrinology Unit, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, IMSS, Mexico City, Mexico

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Lourdes-Josefina Balcazar-Hernandez Endocrinology Service and Experimental Endocrinology Unit, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, IMSS, Mexico City, Mexico

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Virgilio Melgar Neurological Center

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Roser-Montserrat Magriña-Mercado Endocrinology Service and Experimental Endocrinology Unit, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, IMSS, Mexico City, Mexico

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Baldomero Gonzalez Endocrinology Service and Experimental Endocrinology Unit, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, IMSS, Mexico City, Mexico

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Javier Baquera Pathology Department, American British Cowdray Hospital, Mexico City, Mexico

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Moisés Mercado Endocrinology Service and Experimental Endocrinology Unit, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, IMSS, Mexico City, Mexico
Neurological Center

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A 19-year-old woman with a history of isosexual precocious puberty and bilateral oophorectomy at age 10 years because of giant ovarian cysts, presents with headaches and mild symptoms and signs of hyperthyroidism. Hormonal evaluation revealed elevated FSH and LH levels in the postmenopausal range and free hyperthyroxinemia with an inappropriately normal TSH. Pituitary MRI showed a 2-cm macroadenoma with suprasellar extension. She underwent successful surgical resection of the pituitary tumor, which proved to be composed of two distinct populations of cells, each of them strongly immunoreactive for FSH and TSH, respectively. This mixed adenoma resulted in two different hormonal hypersecretion syndromes: the first one during childhood and consisting of central precocious puberty and ovarian hyperstimulation due to the excessive secretion of biologically active FSH and which was not investigated in detail and 10 years later, central hyperthyroidism due to inappropriate secretion of biologically active TSH. Although infrequent, two cases of isosexual central precocious puberty in girls due to biologically active FSH secreted by a pituitary adenoma have been previously reported in the literature. However, this is the first reported case of a mixed adenoma capable of secreting both, biologically active FSH and TSH.

Learning points:

  • Although functioning gonadotrophinomas are infrequent, they should be included in the differential diagnosis of isosexual central precocious puberty.

  • Some functioning gonadotrophinomas are mixed adenomas, secreting other biologically active hormones besides FSH, such as TSH.

  • Early recognition and appropriate treatment of these tumors by transsphenoidal surgery is crucial in order to avoid unnecessary therapeutic interventions that may irreversibly compromise gonadal function.

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Jeremy M W Kirk Department of Endocrinology, Birmingham Children's Hospital, Steelhouse Lane, Birmingham, B4 6NH, UK

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Nalin Wickramasuriya Department of Endocrinology, Birmingham Children's Hospital, Steelhouse Lane, Birmingham, B4 6NH, UK

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Nicholas J Shaw Department of Endocrinology, Birmingham Children's Hospital, Steelhouse Lane, Birmingham, B4 6NH, UK

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Summary

Estrogen is used to induce puberty in peripubertal girls with hypogonadism. Although both synthetic and natural forms are available, along with different routes of administration, in the UK oral ethinyl estradiol and the low-dose oral contraceptive pill are commonly used as hormone replacement therapy for practical reasons. We present five peripubertal girls (aged 12.5–14.9 years) with hypogonadism (two with primary hypogonadism due to Turner syndrome and three with central (secondary) hypogonadism as part of multiple pituitary hormone deficiency) who for a variety of reasons have received milligram doses of estradiol (E2) in error for between 6 weeks and 6 months, instead of the expected microgram doses of ethinyl estradiol. Although there are no direct comparisons in peripubertal girls between synthetic and natural estrogens, all girls had vaginal bleeding whilst receiving the milligram doses and have ended up with reduced final heights, below the 9th centile in 1 and below the 2nd centile in 4. Whilst reduction in final height may be part of the underlying condition (especially in Turner syndrome) the two girls with height predictions performed prior to receiving the estrogen overdose have not achieved their predicted height. Estrogen is one of the few drugs which is available in both milligram and microgram formulations. Clinicians need to be alert to the possibility of patients receiving the wrong formulation and dosage in error.

Learning points

  • Girls with primary and secondary gonadal failure require assistance with pubertal induction.

  • Although several different formulations and route of administration are available, for practical reasons, the majority of girls in the UK receive oral ethinyl estradiol.

  • Estrogen preparations are available in both milligram and microgram formulations, with potential for receiving the wrong dose.

  • Girls receiving milligram rather than microgram preparations all had vaginal bleeding and a short final height.

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