What symptoms should be looked for in a female patient with hyperandrogenism to suspect prolactinoma or adrenal tumors?

Symptoms to Suspect Prolactinoma or Adrenal Tumors in Female Patients with Hyperandrogenism

In a female patient with hyperandrogenism, suspect prolactinoma if menstrual disturbances, galactorrhea, or delayed puberty are present, and suspect adrenal tumors when testosterone levels exceed 150-200 ng/dL, DHEAS is markedly elevated (>700 μg/dL), or virilization develops rapidly over weeks to months. 1

Key Clinical Features Suggesting Prolactinoma

Reproductive and Hormonal Manifestations

• Menstrual disturbances including oligomenorrhea, primary amenorrhea, or secondary amenorrhea are cardinal features of prolactinoma, as elevated prolactin inhibits gonadotropin secretion via suppression of kisspeptin 2
• Galactorrhea (inappropriate breast milk production) is a highly specific sign that should prompt immediate prolactin measurement 2
• Delayed or arrested puberty occurring more than 2 standard deviations later than the mean population age for sex suggests prolactinoma, particularly in adolescents 2

Mass Effect Symptoms

• Headache and visual field loss indicate macroprolactinoma with mass effect on surrounding structures, occurring more commonly in males but still important in females 2
• Growth failure or short stature may occur when macroprolactinomas compromise normal pituitary function 2

Important Clinical Context

• Prolactinomas are the most common pituitary adenoma type, with 93% presenting after age 12 years and occurring 3-4.5 times more frequently in females 2
• Weight gain is reported in 23% of patients with macroprolactinomas who had obesity at diagnosis 2

Key Clinical Features Suggesting Adrenal Tumors

Biochemical Red Flags

• Testosterone levels >150-200 ng/dL strongly suggest an androgen-secreting tumor rather than PCOS, which typically causes only mild-to-moderate elevations 1
• DHEAS levels >700 μg/dL point toward an adrenal source of androgen excess and raise concern for adrenocortical carcinoma 1, 3
• Rapid symptom onset developing over weeks to months (rather than years) is characteristic of tumors versus functional disorders 1

Virilization Signs (Severe Androgen Excess)

• Clitoromegaly (clitoral enlargement) indicates severe androgen excess rarely seen with PCOS and warrants urgent tumor evaluation 1, 3, 4
• Deepening of the voice occurs with androgen-secreting tumors in patients with severe hyperandrogenism 3
• Male-pattern baldness (androgenic alopecia) beyond typical female-pattern hair loss suggests significant androgen excess 1, 3
• Increased muscle mass with masculine body habitus indicates virilization 1

Associated Features Suggesting Adrenal Pathology

• Cushing syndrome features (central obesity, moon facies, striae, hypertension) alongside hyperandrogenism strongly suggest adrenal pathology, as approximately 60% of adrenocortical carcinomas present with hormone excess 1, 5
• Worsening acne and hirsutism that is severe, persistent, or resistant to standard treatments, particularly when accompanied by other virilization signs 3, 6, 5

Diagnostic Algorithm for Suspected Tumors

When to Measure Prolactin

• Measure serum prolactin in any female patient with hyperandrogenism who has menstrual disturbances, galactorrhea, delayed puberty, or visual symptoms 2, 3
• A single prolactin measurement at any time of day is sufficient for initial assessment 2
• If modestly elevated (up to 5 times upper limit of normal), repeat with serial measurements using an indwelling cannula to exclude stress-related elevation 2

When to Suspect and Image for Adrenal/Ovarian Tumors

• Measure total testosterone by LC-MS/MS and DHEAS as first-line tests to differentiate ovarian from adrenal sources 1, 3
• Perform CT or MRI of abdomen and pelvis urgently when testosterone >150-200 ng/dL, DHEAS >700 μg/dL, or any virilization is present 1
• Do not delay evaluation when virilization is present, as this always warrants urgent investigation regardless of age 1

Imaging Interpretation for Adrenal Masses

• Adrenal tumors >5 cm, inhomogeneous appearance, irregular margins, or local invasion suggest adrenocortical carcinoma 1
• Hounsfield units ≥10 HU on non-contrast CT raise concern for pheochromocytoma or malignancy and require further evaluation, including pheochromocytoma screening 1
• Tumors >3 cm for aldosterone-secreting or >5 cm for cortisol-secreting lesions with irregular morphology or lipid-poor characteristics suggest malignancy 1

Critical Pitfalls to Avoid

• Do not attribute rapid-onset virilization to PCOS, which typically presents with gradual symptom development over years 1, 3
• Do not miss co-secreting tumors: adrenal masses can secrete both cortisol and androgens, requiring comprehensive hormonal evaluation 5
• Do not forget to screen for pheochromocytoma in patients with adrenal masses ≥10 HU, as these can co-secrete androgens 1
• Do not overlook non-classic congenital adrenal hyperplasia (NCCAH) in younger women with moderate hyperandrogenism, which should be considered in the differential 1