Differentials
Common
Prolactinoma
History
symptoms of hyperprolactinaemia in both sexes (galactorrhoea, infertility, decreased libido, sexual dysfunction, osteoporosis), in women (oligo/amenorrhoea, menstrual disturbances, hirsutism, vaginal dryness, dyspareunia, acne), in men (erectile dysfunction, gynaecomastia), in children (delayed puberty in both sexes; primary amenorrhoea, galactorrhoea in girls); symptoms of 'mass effect' (headaches, visual loss, seizures)
Exam
signs of hyperprolactinaemia (hirsutism and acne in women, gynaecomastia 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 or >2000 milliunits/L, macroprolactinomas >250 micrograms/L or >5000 milliunits/L
More - serum electrolytes and creatinine:
within normal range
More - urea:
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 (adrenocorticotrophic hormone, luteinising 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 sulphate:
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 goitre; cool, rough, and dry skin; puffy face and hands; husky voice; slow reflexes; thin and brittle nails; carotenaemic skin colour
1st investigation
- serum prolactin (PRL):
<50 micrograms/L or <1000 milliunits/L
- thyroid-stimulating hormone:
elevated
- free thyroxine:
decreased
Other investigations
Drug-induced hyperprolactinaemia
History
use of drugs known to elevate prolactin (PRL) (antipsychotics, antidepressants, opioids, cocaine, antihypertensives, gastrointestinal drugs, oestrogens, excessive alcohol intake), past medical history of conditions requiring these drugs
Exam
non-specific findings
1st investigation
- serum prolactin (PRL):
<100 micrograms/L or <2000 milliunits/L
More
Other investigations
Macroprolactinaemia
History
usually asymptomatic; rarely presents with galactorrhoea, amenorrhoea, and infertility
Exam
non-specific findings
1st investigation
- serum prolactin (PRL):
usually <100 micrograms/L or <2000 milliunits/L
More
Other investigations
- polyethylene glycol (PEG) precipitation:
percentage recovery of PRL between 40% and 60%
More
Pregnancy
History
amenorrhoea, nausea and vomiting, breast enlargement
Exam
most women appear clinically well, abdomino-pelvic examination may reveal gravid uterus
1st investigation
- serum prolactin (PRL):
200-500 micrograms/L or 4000-10,000 milliunits/L
More - pregnancy test:
positive
Other investigations
Idiopathic hyperprolactinaemia
History
exclusion of pathological, physiological, and pharmacological aetiologies of hyperprolactinaemia
Exam
non-specific findings
1st investigation
- serum prolactin (PRL):
usually <100 micrograms/L or 2000 milliunits/L
More
Other investigations
- polyethylene glycol (PEG) precipitation:
percentage recovery of PRL between 40% and 60%
More
Uncommon
Acromegaly
History
symptoms of acromegaly (fatigue, paraesthesias, increased sweating, joint pain); symptoms of hyperprolactinaemia in both sexes (galactorrhoea, infertility, decreased libido, sexual dysfunction, osteoporosis), in women (oligo/amenorrhoea, menstrual disturbances, hirsutism, vaginal dryness, dyspareunia, acne), in men (erectile dysfunction, gynaecomastia); symptoms of 'mass effect' (headaches, visual loss, seizures)
Exam
signs of acromegaly (acral enlargement, e.g., hands; tissue overgrowth, weight gain, thyroid goitre, hypertension); signs of hyperprolactinaemia (hirsutism and acne in women, gynaecomastia in men); signs of mass effect (visual field defects, cranial nerve neuropathies)
1st investigation
- serum prolactin (PRL):
usually >200 micrograms/L or >4000 milliunits/L
More
Hypothalamic mass compressing pituitary stalk
History
symptoms of hyperprolactinaemia in both sexes (galactorrhoea, infertility, decreased libido, sexual dysfunction, osteoporosis), in women (oligo/amenorrhoea, menstrual disturbances, hirsutism, vaginal dryness, dyspareunia, acne), in men (erectile dysfunction, gynaecomastia), in children (delayed puberty in both sexes; primary amenorrhoea, galactorrhoea in girls); symptoms of 'mass effect' (headaches, visual loss, seizures)
Exam
signs of hyperprolactinaemia (hirsutism and acne in women, gynaecomastia 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 (adrenocorticotrophic hormone, luteinising 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 sulphate:
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 tumours (insulinomas, gastrinomas), and/or adrenal adenomas; symptoms of hyperprolactinaemia (renal stones, polyuria, polydipsia, osteomalacia or rickets, fatigue, depression, constipation); symptoms of hyperprolactinaemia in both sexes (galactorrhoea, infertility, decreased libido, sexual dysfunction, osteoporosis), in women (oligo/amenorrhoea, menstrual disturbances, hirsutism, vaginal dryness, dyspareunia, acne), in men (erectile dysfunction, gynaecomastia), in children (delayed puberty in both sexes; primary amenorrhoea, galactorrhoea in girls); symptoms of 'mass effect' (headaches, visual loss, seizures)
Exam
signs of hyperparathyroidism, insulinomas (hypoglycaemia), gastrinomas (gastric ulcers, Zollinger-Ellison syndrome), and/or adrenal adenomas (hypertension, Cushing syndrome); signs of hyperprolactinaemia (hirsutism and acne in women, gynaecomastia 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 or >2000 milliunits/L, macroprolactinomas >250 micrograms/L or >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 tumours, adrenal adenomas
Traumatic sectioning of pituitary stalk
History
history of surgery or radiotherapy for brain tumours; symptoms of hyperprolactinaemia in both sexes (galactorrhoea, infertility, decreased libido, sexual dysfunction, osteoporosis), in women (oligo/amenorrhoea, menstrual disturbances, hirsutism, vaginal dryness, dyspareunia, acne), in men (erectile dysfunction, gynaecomastia); symptoms of 'mass effect' (headaches, visual loss, seizures); symptoms of arginine vasopressin deficiency (AVP-D; previously known as central diabetes insipidus [polyuria, polydipsia])
Exam
signs of hyperprolactinaemia (hirsutism and acne in women, gynaecomastia 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 or <2000 milliunits/L
More - MRI of the pituitary gland:
evidence of previous surgery/radiotherapy
Other investigations
- urine output:
>2.5 L/day in AVP-D
- serum sodium:
>146 mmol/L (mEq/L) in AVP-D
- antidiuretic hormone:
undetectable in AVP-D
- serum osmolality:
>287 mOsm/kg in AVP-D
- urine osmolality:
<100 mOsm/kg in AVP-D
- urine specific gravity:
<1.005 in AVP-D
- pituitary hormones (adrenocorticotrophic hormone, luteinising 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 sulphate:
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's thyroiditis, adrenal insufficiency in primary adrenal insufficiency, hypocalcaemia in hypoparathyroidism, chronic liver disease in autoimmune hepatitis)
1st investigation
- serum prolactin (PRL):
usually <100 micrograms/L or <2000 milliunits/L
More - thyroid-stimulating hormone:
elevated in Hashimoto's thyroiditis
- free thyroxine:
decreased in Hashimoto's thyroiditis
- anti-thyroid peroxidase auto-antibodies:
positive in Hashimoto's thyroiditis
- serum cortisol:
decreased in primary adrenal insufficiency
- serum sodium:
decreased in primary adrenal insufficiency
- serum potassium:
elevated in primary adrenal insufficiency
- adrenocorticotrophic hormone (ACTH):
elevated in primary adrenal insufficiency
- 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
- adrenocorticotropic hormone (ACTH) stimulation test:
serum cortisol <500 nanomoles/L (<18 micrograms/dL) in primary adrenal insufficiency
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 or <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:
non-caseating granulomas in sarcoidosis and TB, Langerhans cells in histiocytosis X
More - lymph node biopsy:
non-caseating granulomas in sarcoidosis and TB
- skin biopsy:
Langerhans cells in histiocytosis X
- bone marrow biopsy:
Langerhans cells in histiocytosis X
Polycystic ovary syndrome
History
oligomenorrhoea (or anovulation) amenorrhoea
Exam
hirsutism, acne, obesity
1st investigation
- clinical diagnosis:
clinical diagnosis can be made for women with hirsutism and infrequent/reduced menstrual bleeding
- serum prolactin (PRL):
<50 micrograms/L or <1000 milliunits/L
More
Chronic kidney disease
History
history of underlying disease, often due to diabetes and/or hypertension; possible lupus or vasculitis; history of abdominal pain and discomfort
Exam
signs of uraemia (hypertension, yellow skin, uraemic frost [white/yellowish urea crystal depositions on face, neck, and trunk], uraemic fetor, decreased mental status)
1st investigation
- serum prolactin (PRL):
<50 micrograms/L or <1000 milliunits/L
More - serum creatinine:
elevated (>97 micromol/L [1.1 mg/dL] in men, >106 micromol/L [1.2 mg/dL] in women)
Other investigations
- urinalysis:
haematuria 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 oedema, 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 or <1000 milliunits/L
More
Other investigations
Ectopic hyperprolactinaemia
History
may only be diagnosed after exclusion of pathological, physiological, and pharmacological aetiologies of hyperprolactinaemia; symptoms of an extrapituitary tumour (e.g., ovarian)
Exam
signs of an extrapituitary tumour (e.g., ovarian)
1st investigation
- serum prolactin (PRL):
usually <100 micrograms/L or <2000 milliunits/L
More - MRI of the pituitary gland:
no abnormality detected
- CT chest and abdomen:
evidence of extrapituitary tumour
Other investigations
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