Abstract Introduction Primary amenorrhea is a challenging presentation with diverse etiologies, including genetic, endocrine, structural, and chronic systemic diseases. Celiac disease (CD), an autoimmune enteropathy, may manifest with extraintestinal features such as delayed puberty or amenorrhea. We present a case of primary amenorrhea due to CD, diagnosed at the Faiha Specialized Diabetes, Endocrine and Metabolism Center (FDEMC), Basrah, south of Iraq. Clinical Case A 21-year-old female presented in October 2021 with primary amenorrhea. She was the eldest sibling; her mother and sister had normal menarche at 13 years. She denied chronic illness, gastrointestinal symptoms, galactorrhea, or prolonged drug use. Examination revealed a thin female (40 kg, 150 cm, BMI 17.7 kg/m²) with breast Tanner stage II, scant pubic and axillary hair, and otherwise normal systemic findings. Initial investigations showed hypogonadotropic hypogonadism: FSH 0.2 mIU/mL, LH 0.1 mIU/mL, estradiol 2.5 pg/mL. MRI pelvis revealed an infantile uterus, pituitary MRI was normal. Other labs included TSH 3.2 µIU/mL, free T4 1.3 ng/dL, cortisol 17 µg/dL, ACTH 23.4 pg/mL, DHEA-S 272.2 µg/dL, prolactin 9.2 ng/mL, PTH 23.9 pg/mL. DEXA showed low bone mineral density (Z-score −2.8, BMD 0.744 g/cm²). Labs showed Hb 12.9 g/dL, MCV 79 fL, calcium 8.5 mg/dL, vitamin D 19 ng/mL. Anti-tTG (anti-tissue transglutaminase antibody) was negative. Hormone replacement therapy (HRT) with ethinyl estradiol was initiated and titrated for 18 months without improvement; uterine hypoplasia persisted. On reevaluation in October 2023, duodenal biopsy showed villous atrophy with lymphoid hyperplasia (Marsh IIIA), confirming CD. Genetic testing revealed HLA-DQ2 positivity (DQB102, DQA105). Pelvic ultrasound continued to show a hypoplastic uterus. A strict gluten-free diet was initiated alongside HRT due to low bone density. Within 3 months, she reported improved appetite and weight gain (to 50 kg), height increased to 153 cm, breast development advanced to Tanner stage III then stage IV, and vaginal discharge appeared. Spotting began in August 2024, with serial imaging showing progressive uterine growth, reaching near adult size by April 2025. She remains on full adult doses of estradiol with cyclic progesterone. This case highlights CD as an uncommon cause of primary amenorrhea and hypogonadotropic hypogonadism. Diagnosis may be difficult, especially in the absence of gastrointestinal symptoms and with negative serology, as seen in our patient. Biopsy and HLA typing were critical. Extraintestinal manifestations may precede classical symptoms, and failure to respond to HRT should prompt further evaluation. Conclusion Primary amenorrhea can be the first manifestation of CD. In young females with unexplained hypogonadotropic hypogonadism, CD should be considered—even with negative serology. Early recognition and a gluten-free diet may restore endocrine function, promote pubertal progression, and improve reproductive potential.Figure 1:DEXA scan showing low bone mineral density (left) and sagittal pelvic MRI demonstrating an infantile uterus (right) in a 21-year-old female with primary amenorrhea. Table 1:Densitometry DataLumbar spine Z-scores ranged from -2.3 to -2.9, falling below the expected range for age. This finding indicates low bone mass not attributable to physiologic aging and raises concern for secondary osteoporosis, likely related to hypogonadism secondary to celiac disease.”
Zuhairi et al. (Thu,) studied this question.