Reproductive Endocrinology
PCOS and androgen excess
PCOS is diagnosed by the Rotterdam criteria when two of three are present: oligo-ovulation or anovulation, clinical or biochemical hyperandrogenism, and polycystic ovarian morphology. Alternative causes must be excluded, including thyroid disease, hyperprolactinemia, nonclassic congenital adrenal hyperplasia, and Cushing syndrome. Hirsutism is assessed clinically; free testosterone is useful when total testosterone is borderline because sex hormone-binding globulin alters free levels. Treatment is directed at goals: combined oral contraceptives for cycle regulation and androgen excess, metformin for insulin resistance, and letrozole for ovulation induction.
Hypogonadism, menopause, and puberty
Male hypogonadism requires symptoms plus two morning total testosterone measurements. Low testosterone with high LH/FSH indicates primary testicular failure; low or normal LH/FSH indicates central failure. Klinefelter syndrome causes small testes, gynecomastia, elevated gonadotropins, and low testosterone. Turner syndrome causes short stature, primary amenorrhea, elevated FSH, and requires karyotyping. Menopause is clinical in women older than 45 with vasomotor symptoms; FSH testing is not routinely needed. Precocious puberty is evaluated with a GnRH stimulation test. Infertility evaluation includes semen analysis, ovulation assessment, and tubal patency.
Traps and worked example
Do not diagnose PCOS by ultrasound alone, and remember that combined oral contraceptives raise sex hormone-binding globulin and lower free testosterone. A 28-year-old with oligomenorrhea, hirsutism, normal TSH and prolactin, elevated free testosterone, and polycystic ovaries meets PCOS criteria after exclusion of other causes. Rule of thumb: confirm male testosterone deficiency with two morning total testosterone levels before treatment.
Bone and Mineral Metabolism
Calcium and parathyroid interpretation
Interpret calcium with albumin: corrected calcium = measured calcium + 0.8 × (4.0 − albumin). Primary hyperparathyroidism causes high calcium with high or inappropriately normal PTH and low phosphate. Hypercalcemia of malignancy typically has low PTH and may show elevated PTHrP. Familial hypocalciuric hypercalcemia is distinguished by low 24-hour urine calcium and a low calcium-to-creatinine clearance ratio. Hypocalcemia with low PTH suggests hypoparathyroidism; hypocalcemia with high PTH suggests vitamin D deficiency or renal disease. Check magnesium in hypocalcemia because hypomagnesemia impairs PTH secretion and action.
Osteoporosis and metabolic bone disease
Osteoporosis is diagnosed by DXA T-score ≤−2.5 at the hip or spine, or by a fragility fracture. Osteopenia is a T-score between −1.0 and −2.5; FRAX estimates fracture risk and guides treatment. Bisphosphonates are first-line for most patients but are avoided with eGFR <30–35 mL/min/1.73 m² and untreated hypocalcemia. Denosumab requires adherence and carries rebound vertebral fracture risk after discontinuation. Teriparatide is anabolic and is avoided in Paget disease or prior skeletal malignancy. Paget disease often shows isolated alkaline phosphatase elevation with normal calcium and phosphate. Osteomalacia shows low vitamin D, low calcium and phosphate, high PTH, and high alkaline phosphatase.
Trap and worked example
A patient with calcium 10.8 mg/dL and albumin 3.0 g/dL has corrected calcium 11.6 mg/dL; an intact PTH of 80 pg/mL is inappropriately high and indicates primary hyperparathyroidism. Rule of thumb: always correct calcium for albumin before interpreting PTH.