Background and receptor biology: Androgen insensitivity syndrome (AIS) is a rare 46,XY disorder of sex development spanning a phenotypic continuum from a complete external female phenotype through genital ambiguity to isolated gynaecomastia. The androgen receptor (AR) gene maps to the long arm of the X chromosome (Xq11–12); androgen-mediated transcription is coded by the C-terminus of the ligand-binding domain. Loss-of-function mutations alter the receptor, producing inefficient androgen binding and failure of downstream androgen action. The result is the defining translational paradox of complete AIS (CAIS): testes that secrete testosterone and anti-Müllerian hormone normally, Müllerian regression that proceeds unimpeded, but Wolffian development and virilisation that fail entirely — a natural human model of androgen action that is best understood by mapping receptor pathophysiology directly onto each bedside decision.

Clinical illustration: We present two sisters diagnosed with CAIS. Case 1, a 17-year-old reared as female, presented with primary amenorrhoea and poor secondary sexual development, with prior right inguinal hernia repair at age 3 and a palpable left inguinal gonad. Sexual maturity rating was Tanner I for axillary and pubic hair with Tanner V breast development. Karyotype was 46,XY; LH 65 mIU/mL, FSH 39 mIU/mL, testosterone 23.92 nmol/L (690 ng/dL). Ultrasonography showed a left iliac-fossa gonad and a retrovesical prostate-like structure with no Müllerian derivatives. She had been empirically started on a combined oestrogen–progesterone pill for six months before referral. Detailed family history prompted evaluation of her 15-year-old sister (Case 2): Tanner I pubic/axillary hair, Tanner III breast, bilateral palpable inguinal gonads, 46,XY karyotype, LH 15 mIU/mL, FSH 23 mIU/mL, testosterone 42.1 nmol/L (1217 ng/dL), rudimentary prostate and absent Müllerian structures. Case 1 underwent left gonadectomy; histopathology confirmed testicular tissue without spermatogenesis. She is maintained on estradiol valerate 0.5 mg daily with metabolic surveillance at each visit. Case 2 is on follow-up awaiting gonadectomy.

Bedside decisions: Four translational themes emerge. First, diagnosis without genotype: AR sequencing was unaffordable for this family, yet CAIS can be reliably diagnosed from a 46,XY karyotype with female external phenotype, imaging showing testes with absent or degenerated Müllerian remnants, and normal-to-elevated testosterone with normal-to-raised LH. Second, the missed window: inguinal hernia in a phenotypic girl carries an estimated 0.8–2.4% probability of CAIS, and earlier surgical suspicion would have diagnosed Case 1 fourteen years sooner. Third, gonadal risk: germ-cell tumour incidence is reported at 0.8% in CAIS and 5.5% across AIS, rising progressively after puberty and reaching up to 33% by the fifth decade — the central determinant of gonadectomy timing and of subsequent oestrogen replacement. Fourth, family history as a diagnostic instrument, as in previously reported sibling and maternal-aunt clusters.

Conclusion: CAIS must remain a standing differential in primary amenorrhoea, and hormonal therapy should never precede evaluation. Early diagnosis enables timely gonadectomy and structured oestrogen replacement, while the profound psychosocial impact on patient and family — particularly in conservative sociocultural settings — demands formal assessment as a routine component of care.

She is a prominent Indian endocrinologist, diabetologist, and clinical researcher serving as an Assistant Professor in the Department of Endocrinology at the historic SCB Medical College and Hospital in Cuttack, Odisha. Born in 1981, she has dedicated her medical career to advancing the understanding of complex metabolic and hormonal disorders. Her extensively published research focuses on critical areas of endocrinology, including the diagnostic differentiation between Isolated Hypogonadotropic Hypogonadism and Constitutional Delay of Growth and Puberty, insulin resistance patterns, and vascular complications in Type 1 Diabetes Mellitus patients. She is also widely recognized for her clinical investigations into thyroid dysfunctions, specifically optimizing rapid differential diagnoses for thyrotoxicosis and tracking metabolic variations in subclinical hypothyroid cases. Through her dual roles in academic research and active patient care, she contributes significantly to contemporary endocrine medicine in India.