Differentials
Common
Prolactinoma
History
symptoms of hyperprolactinemia in both sexes (galactorrhea, infertility, decreased libido, sexual dysfunction, osteoporosis), in women (oligo/amenorrhea, menstrual disturbances, hirsutism, vaginal dryness, dyspareunia, habitual abortions, acne), in men (erectile dysfunction, gynecomastia), in children (delayed puberty in both sexes; primary amenorrhea, galactorrhea in girls); symptoms of "mass effect" (headaches, visual loss, seizures)
Exam
signs of hyperprolactinemia (hirsutism and acne in women, gynecomastia in men); signs of mass effect (visual field defects, cranial nerve neuropathies); signs of hypogonadism (testicular size and texture, pattern of body hair growth)
1st investigation
- serum prolactin (PRL):
usually >100 micrograms/L (2000 milliunits/L), macroprolactinomas >250 micrograms/L (5000 milliunits/L)
More - serum electrolytes and creatinine:
within normal range
More - blood urea nitrogen:
within normal range
More - liver function tests and albumin:
within normal range
More - prothrombin time:
within normal range
More - thyroid-stimulating hormone and free thyroxine:
within normal range
More - pregnancy test:
negative
More
Other investigations
- polyethylene glycol (PEG) precipitation:
negative
More - MRI of the pituitary gland:
micro- or macroprolactinoma
More - pituitary hormones (adrenocorticotropic hormone, luteinizing hormone, follicle-stimulating hormone, growth hormone):
decreased in hypopituitarism
More - glucose tolerance test:
decreased in hypopituitarism
More - cortisol:
decreased in hypopituitarism
More - serum testosterone:
decreased in hypopituitarism
More - serum estradiol:
decreased in hypopituitarism
More - serum dehydroepiandrosterone sulfate:
decreased in hypopituitarism
More - insulin-like growth factor 1:
decreased in hypopituitarism
More
Primary hypothyroidism
History
fatigue, sensitivity to cold, constipation, menstrual abnormalities (particularly menorrhagia), muscle cramps, weight gain
Exam
thyroid goiter; cool, rough, and dry skin; puffy face and hands; husky voice; slow reflexes; thin and brittle nails; carotenemic skin color
1st investigation
- serum prolactin:
<50 micrograms/L (1000 milliunits/L)
- thyroid-stimulating hormone:
elevated
- free thyroxine:
decreased
Other investigations
Drug-induced hyperprolactinemia
History
use of drugs known to elevate prolactin (PRL) (antipsychotics, antidepressants, opiates, cocaine, antihypertensives, gastrointestinal medications, estrogens, excessive alcohol intake), past medical history of conditions requiring these medications
Exam
nonspecific findings
1st investigation
- serum PRL:
usually <100 micrograms/L (2000 milliunits/L)
More
Other investigations
Macroprolactinemia
History
usually asymptomatic; rarely presents with galactorrhea, amenorrhea, and infertility
Exam
nonspecific findings
1st investigation
- serum prolactin (PRL):
usually <100 micrograms/L (2000 milliunits/L)
More
Other investigations
- polyethylene glycol (PEG) precipitation:
percentage recovery of PRL between 40% and 60%
More
Pregnancy
History
amenorrhea, nausea and vomiting, breast enlargement
Exam
nonspecific findings
1st investigation
- serum prolactin (PRL):
200-500 micrograms/L (4000-10,000 milliunits/L)
More - pregnancy test:
positive
Other investigations
Uncommon
Acromegaly
History
symptoms of acromegaly (fatigue, paresthesias, increased sweating, joint pain); symptoms of hyperprolactinemia in both sexes (galactorrhea, infertility, decreased libido, sexual dysfunction, osteoporosis), in women (oligo/amenorrhea, menstrual disturbances, hirsutism, vaginal dryness, dyspareunia, habitual abortions, acne), in men (erectile dysfunction, gynecomastia); symptoms of "mass effect" (headaches, visual loss, seizures)
Exam
signs of acromegaly (acral enlargement, e.g., hands; tissue overgrowth, weight gain, thyroid goiter, hypertension); signs of hyperprolactinemia (hirsutism and acne in women, gynecomastia in men); signs of mass effect (visual field defects, cranial nerve neuropathies)
1st investigation
- serum prolactin (PRL):
usually >200 micrograms/L (4000 milliunits/L)
More
Hypothalamic mass compressing pituitary stalk
History
symptoms of hyperprolactinemia in both sexes (galactorrhea, infertility, decreased libido, sexual dysfunction, osteoporosis), in women (oligo/amenorrhea, menstrual disturbances, hirsutism, vaginal dryness, dyspareunia, habitual abortions, acne), in men (erectile dysfunction, gynecomastia), in children (delayed puberty in both sexes; primary amenorrhea, galactorrhea in girls); symptoms of "mass effect" (headaches, visual loss, seizures)
Exam
signs of hyperprolactinemia (hirsutism and acne in women, gynecomastia in men); signs of mass effect (visual field defects, cranial nerve neuropathies); signs of hypogonadism (testicular size and texture, pattern of body hair growth)
1st investigation
Other investigations
- pituitary hormones (adrenocorticotropic hormone, luteinizing hormone, follicle-stimulating hormone, growth hormone):
decreased in hypopituitarism
More - glucose tolerance test:
decreased in hypopituitarism
More - cortisol:
decreased in hypopituitarism
More - serum testosterone:
decreased in hypopituitarism
More - serum estradiol:
decreased in hypopituitarism
More - serum dehydroepiandrosterone sulfate:
decreased in hypopituitarism
More - insulin-like growth factor 1:
decreased in hypopituitarism
More
Multiple endocrine neoplasia syndrome type I (MEN I)
History
history of hyperparathyroidism, enteropancreatic tumors (insulinomas, gastrinomas), and/or adrenal adenomas; symptoms of hyperprolactinemia (renal stones, polyuria, polydipsia, osteomalacia or rickets, fatigue, depression, constipation); symptoms of hyperprolactinemia in both sexes (galactorrhea, infertility, decreased libido, sexual dysfunction, osteoporosis), in women (oligo/amenorrhea, menstrual disturbances, hirsutism, vaginal dryness, dyspareunia, habitual abortions, acne), in men (erectile dysfunction, gynecomastia), in children (delayed puberty in both sexes; primary amenorrhea, galactorrhea in girls); symptoms of "mass effect" (headaches, visual loss, seizures)
Exam
signs of hyperparathyroidism, insulinomas (hypoglycemia), gastrinomas (gastric ulcers, Zollinger-Ellison syndrome), and/or adrenal adenomas (hypertension, Cushing syndrome); signs of hyperprolactinemia (hirsutism and acne in women, gynecomastia in men); signs of mass effect (visual field defects, cranial nerve neuropathies); signs of hypogonadism (testicular size and texture, pattern of body hair growth)
1st investigation
- serum prolactin (PRL):
usually >100 micrograms/L (2000 milliunits/L), macroprolactinomas >250 micrograms/L (5000 milliunits/L)
More - MRI of the pituitary gland:
micro- or macroprolactinoma
More - serum calcium:
elevated in hyperparathyroidism
- parathyroid hormone:
elevated in hyperparathyroidism
- serum cortisol:
elevated, loss of diurnal rhythm in Cushing syndrome
More - urinary cortisol:
elevated in Cushing syndrome
- aldosterone/plasma renin activity ratio:
elevated (>30) in adrenal adenoma
More - serum aldosterone:
elevated in adrenal adenoma
More - plasma renin activity:
suppressed in adrenal adenoma
More
Other investigations
- overnight suppression test:
failure of morning cortisol suppression in Cushing syndrome
More - genetic testing:
positive for menin gene (chromosome 11q13)
More - sestamibi scintigraphy:
positive in primary hyperparathyroidism
- renal ultrasound:
evidence of adrenal adenoma
- fasting gastrin:
elevated in gastrinomas
- fasting insulin:
elevated in insulinomas
- CT or MRI scan abdomen:
evidence of enteropancreatic tumors, adrenal adenomas
Traumatic sectioning of pituitary stalk
History
history of surgery or radiation therapy for brain tumors; symptoms of hyperprolactinemia in both sexes (galactorrhea, infertility, decreased libido, sexual dysfunction, osteoporosis), in women (oligo/amenorrhea, menstrual disturbances, hirsutism, vaginal dryness, dyspareunia, habitual abortions, acne), in men (erectile dysfunction, gynecomastia); symptoms of "mass effect" (headaches, visual loss, seizures); symptoms of diabetes insipidus (polyuria, polydipsia)
Exam
signs of hyperprolactinemia (hirsutism and acne in women, gynecomastia in men), signs of mass effect (visual field defects, cranial nerve neuropathies), signs of hypogonadism (testicular size and texture, pattern of body hair growth)
1st investigation
- serum prolactin (PRL):
usually <100 micrograms/L (2000 milliunits/L)
More - MRI of the pituitary gland:
evidence of previous surgery/radiation therapy
Other investigations
- urine output:
>2.5 L/day in diabetes insipidus
- serum sodium:
>146 mmol/L (mEq/L) in diabetes insipidus
- antidiuretic hormone:
undetectable in diabetes insipidus
- serum osmolality:
>287 mOsm/kg in diabetes insipidus
- urine osmolality:
<100 mOsm/kg in diabetes insipidus
- urine specific gravity:
<1.005 in diabetes insipidus
- pituitary hormones (adrenocorticotropic hormone, luteinizing hormone, follicle-stimulating hormone, growth hormone):
decreased in hypopituitarism
More - glucose tolerance test:
decreased in hypopituitarism
More - cortisol:
decreased in hypopituitarism
More - serum testosterone:
decreased in hypopituitarism
More - serum estradiol:
decreased in hypopituitarism
More - serum dehydroepiandrosterone sulfate:
decreased in hypopituitarism
More - insulin-like growth factor 1:
decreased in hypopituitarism
More
Lymphocytic hypophysitis
History
Exam
features of associated autoimmune disease (e.g., signs of hypothyroidism in Hashimoto thyroiditis, adrenal insufficiency in Addison disease, hypocalcemia in hypoparathyroidism, chronic liver disease in autoimmune hepatitis)
1st investigation
- serum prolactin (PRL):
usually <100 micrograms/L (2000 milliunits/L)
More - thyroid-stimulating hormone:
elevated in Hashimoto thyroiditis
- free thyroxine:
decreased in Hashimoto thyroiditis
- antithyroid peroxidase autoantibodies:
positive in Hashimoto thyroiditis
- serum cortisol:
decreased in Addison disease
- serum sodium:
decreased in Addison disease
- serum potassium:
elevated in Addison disease
- adrenocorticotropic hormone (ACTH):
elevated in Addison disease
- fasting glucose:
elevated in type 1 diabetes mellitus
- serum calcium:
decreased in hypoparathyroidism
- parathyroid hormone:
decreased in hypoparathyroidism
- aminotransferases:
aspartate aminotransferase elevated, alanine aminotransferase elevated in autoimmune hepatitis
- antinuclear antibodies:
positive in autoimmune hepatitis
- anti-smooth muscle antibodies:
positive in autoimmune hepatitis
- serum IgG:
elevated in autoimmune hepatitis
Other investigations
- synacthen test:
positive in Addison disease
More
Granulomatous hypophysitis
History
history of systemic granulomatous disease (e.g., sarcoidosis, tuberculosis [TB], syphilis, or histiocytosis X)
Exam
signs of systemic granulomatous disease (sarcoidosis and TB: pyrexia, weight loss, lymphadenopathy, crackles on auscultation, shortness of breath, hepatosplenomegaly; syphilis: solitary painless chancre at site of infection, condyloma latum [flat skin lesion in moist skin folds], diffuse rash; histiocytosis X: bony tenderness, pyrexia, weight loss, shortness of breath)
1st investigation
- serum prolactin (PRL):
usually <100 micrograms/L (2000 milliunits/L)
More - serum ACE:
elevated in sarcoidosis
- chest x-ray (CXR):
lung infiltration, hilar and mediastinal lymphadenopathy in sarcoidosis, TB, and histiocytosis X
More - skeletal survey:
lytic lesions in histiocytosis X
- sputum smear and culture:
smear positive for acid-fast bacilli, growth of mycobacteria on culture in TB
More - tuberculin skin testing:
positive in TB
More - Venereal Disease Research Laboratory (VDRL) test:
positive in syphilis
More - rapid plasma reagin:
positive in syphilis
More
Other investigations
- high-resolution CT chest:
lung infiltration, hilar and mediastinal lymphadenopathy in sarcoidosis and histiocytosis X
More - transbronchial biopsy:
noncaseating granulomas in sarcoidosis and TB, Langerhans cells in histiocytosis X
More - lymph node biopsy:
noncaseating granulomas in sarcoidosis and TB
- skin biopsy:
Langerhans cells in histiocytosis X
- bone marrow biopsy:
Langerhans cells in histiocytosis X
Polycystic ovary syndrome
History
oligomenorrhea (or anovulation) amenorrhea
Exam
hirsutism, acne, obesity
1st investigation
- serum prolactin (PRL):
<50 micrograms/L (1000 milliunits/L)
More
Other investigations
- ultrasound of ovaries:
polycystic ovaries
- serum total and free testosterone:
elevated
- serum dehydroepiandrosterone sulfate:
elevated
- serum sex hormone-binding globulin:
decreased
- serum luteinizing hormone/follicle-stimulating hormone ratio:
elevated
- insulin:
elevated
Chronic kidney disease
History
past medical history of chronic renal failure and dialysis
Exam
signs of uremia (hypertension, yellow skin, uremic frost [white/yellowish urea crystal depositions on face, neck and trunk], uremic fetor, decreased mental status)
1st investigation
- serum prolactin (PRL):
<50 micrograms/L (1000 milliunits/L)
More - serum creatinine:
elevated (>1.1 mg/dL in men, >1.2 mg/dL in women)
Other investigations
- urinalysis:
hematuria and/or proteinuria
- ultrasound of kidneys:
small size, presence of obstruction/hydronephrosis, kidney stones
Cirrhosis
History
past medical history of chronic liver disease (e.g., hepatitis B or C viral infection, alcohol abuse, primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis)
Exam
hepatosplenomegaly, weight loss, ascites, jaundice, peripheral edema, encephalopathy, pyrexia, dilation of superficial veins
1st investigation
Other investigations
- abdominal ultrasound:
small liver with nodular surface; possible ascites, splenomegaly, dilated portal vein
Chest wall trauma or surgery
History
history of trauma or surgery to chest wall
Exam
signs of trauma (e.g., burns, bruising), surgical scars on chest wall
1st investigation
- serum prolactin (PRL):
usually <50 micrograms/L (1000 milliunits/L)
More
Other investigations
Ectopic hyperprolactinemia
History
exclusion of pathologic, physiologic and pharmacologic etiologies of hyperprolactinemia
Exam
signs of an extrapituitary tumor (e.g., ovarian)
1st investigation
- serum prolactin (PRL):
usually <100 micrograms/L (2000 milliunits/L)
More - MRI of the pituitary gland:
no abnormality detected
- CT chest and abdomen:
evidence of extrapituitary tumor
Other investigations
Idiopathic hyperprolactinemia
History
exclusion of pathologic, physiologic, and pharmacologic etiologies of hyperprolactinemia
Exam
nonspecific findings
1st investigation
- serum prolactin (PRL):
usually <100 micrograms/L (2000 milliunits/L)
More
Other investigations
- polyethylene glycol (PEG) precipitation:
percentage recovery of PRL between 40% and 60%
More
Use of this content is subject to our disclaimer