A 35-year-old Asian woman, born from non-consanguineous parents, was referred to the department of endocrinology for evaluation of a patient with multiple fragility fractures, and severe osteoporosis accompanied by diffuse goiter. The patient was an ex-smoker and non-drinker. She was 1.71 m tall and weighed 51.2 kg with a body mass index (BMI) of 17.5 kg/m
2. The diagnosis of IHH was established by suggestive clinical findings with primary amenorrhea and absence of growth and development of secondary sexual characteristics and laboratory findings at 16 years. The patient had no facial anomaly or olfactory complaints. No familial history of anosmia, delayed puberty or hypogonadism was reported by the patient. The karyotype was 46XX and genetic screening for mutations in the hypogonadotropic hypogonadism genes was not performed. At that time, anterior pituitary function was preserved except for gonadotropin secretion. The patient has been treated with estrogen replacement since she was 16 years old, but she was taken off estrogen by herself several years ago. Sella magnetic resonance imaging scan revealed a small sized pituitary gland without mass-like lesion and thinning of the lower half of the pituitary stalk (
Fig. 1A). In the combined pituitary stimulation test at 28 years old, the peak luteinizing hormone (LH) was 1.79 IU/L and peak follicle stimulating hormone (FSH) was 1.50 IU/L, suggesting hypogonadotropic hypogonadism (
Table 1). In the recent visit, the patient's blood pressure was 130/82 mmHg and her heart rate was 98 beats/min. On laboratory examination, complete blood count revealed hemoglobin: 12.3 g/dL; leukocyte count: 4.9×10
9/L; and platelet: 313×10
9/L. Serum levels of total cholesterol (207 mg/dL), triglyceride (85 mg/dL), albumin (5.0 g/dL), aspartate transaminase (AST; 22 IU/L), and alanine aminotransferase (ALT; 20 IU/L) were all within normal range. The levels of basal LH, FSH and estradiol were 0.25 IU/L (range, follicular 0.6-6.2; mid-cycle 12-51; luteal 0.0-6.0), 0.23 IU/L (range, follicular 3.3-8.8; mid-cycle 5.4-20; luteal 1.6-8.7), and 10 pg/mL (range, follicular 21-251; mid-cycle 38-649; luteal 21-312), respectively. Symptoms and sign of thyrotoxicosis including tachycardia, smooth skin, and goiter were also developed in the patient. A Technetium-99m (Tc-99m) pertechnetate scintigraphy revealed diffuse enlargement of both lobes of the thyroid gland with markedly increased uptake (
Fig. 1B). A thyroid function test showed newly developed primary hyperthyroidism in the patient (
Table 2). Moreover, the level of thyrotropin binding inhibiting immunoglobulin was also increased (
Table 2). Neck ultrasonography showed an enlarged heterogeneous echogenic thyroid gland with increased vascularity determined by the color doppler method (
Fig. 1C). Serum 25-hydroxy-vitamin D level was also decreased in the patient. The antero-posterior pelvic X-ray showed left proximal femoral fracture (
Fig. 1D) and shoulder X-ray revealed a non-displaced proximal humeral fracture (
Fig. 1E). BMD was measured at the lumbar spine and femoral neck of the patient using dual energy X-ray absorptiometry. The patient had significantly lower BMD at both lumbar spine and femur neck (
Table 3). She was treated with conservative management for humeral fracture and received surgical fixation with screws for the left femoral fracture. The patient was also treated with methimazole, estrogen replacement, calcium, and vitamin D for two years, thereby leading to 2.34% and 6.97% increase in BMD of lumbar spine and femur neck, respectively (
Table 3). She was maintained in an euthyroid state with 2.5 to 5.0 mg of methimazole per day and has been recovering fairly well with estrogen replacement and treatment of calcium and vitamin D 2,000 IU per day for six months (
Table 2).