Case Presentation:

In our Morning Report at WCH, we discussed a case of a patient presenting with features suggestive of testosterone deficiency (fatigue, erectile dysfunction, and reduced libido). Subsequent investigations revealed a culprit prolactinoma.

Learning Points:

1. Clinical Features of early vs late testosterone deficiency
2. Distinguishing between primary and secondary hypogonadism
3. Differential Diagnosis of secondary hypogonadism
4. Local effects of pituitary adenomas
5. Causes of elevated prolactin
6. Management of prolactinoma

Clinical Features of Testosterone Deficiency:

• Manifestations of testosterone deficiency may be classified as:
  • Early: fatigue, reduced libido, erectile dysfunction
  • Late: Hair loss, reduced muscle mass, osteopenia/porosis, gynecomastia
    • note: gynecomastia is more likely to be seen in primary than secondary causes of hypogonadism

Primary vs Secondary Hypogonadism:

• hypogonadism=testes are not serving their usual functions:
  • Impaired spermatogenesis (Sertoli cell function)-under FSH influence
  • Impaired testosterone production (Leydig cell function)-under LH influence
• The location of dysfunction can be delineated based on the pattern of hormonal disturbance
  

Causes of Secondary Hypogonadism:

• 2 major categories of pathology:
  

Local Effects of pituitary adenomas:

• Definitions:
  • microadenoma < 1 cm
  • macroadenoma >1 cm
• Adenomas can be secretory or non-secretory which can lead to systemic effects of hormonal excess (i.e. acromegaly, Cushing’s, hyperthyroidism) or deficiency (i.e. adrenal insufficiency, hypothyroidism)
• Local effects can include any of the following:
  • Raised ICP-related: headache, nausea, vomiting
  • Visual disturbance: related to optic chiasm involvement
    • classic description is bilateral peripheral vision loss-bitemporal hemianopsia
  • Cranial nerve palsies: CN 3, 4, V1, V2 and 6 pass through the cavernous sinus which is situated laterally to the pituitary

Causes of hyperprolactinemia:

• note: the mechanism of elevated prolactin in hypothyroidism relates to the fact that TRH released by the hypothalamus in response to hypothyroidism also triggers prolactin production by the anterior pituitary.

Management of Prolactinoma:

• Indications to treat:
  • Existing/impending neurologic compromise due to size
  • Hypogonadism or other features like galactorrhea in women
  • Extension outside of the sella (superiorly to optic chiasm, lateraly to cavernous sinus, inferior/anteriorly into the sphenoid sinuses)-usually will continue to  enlarge once extension is seen
• 1st line therapy: dopamine agonists (block prolactin secretion)
  • Cabergoline and bromocriptine are the 2 main agents
  • Cabergoline more effectively reduces prolactin levels and has a favourable safety profile (less nausea-inducing than bromocriptine)
  • Note: at higher doses (such as when used for Parkinson’s disease), cabergoline has been associated with the development of valvular heart disease
• Failed medical therapy: trans-sphenoidal surgical resection
  • for large adenomas, adjuvant radiation may also be used

Additional Reading:

1. Schlechte, JA. Prolactinoma. NEJM  2003;349:2035-41.
2. Endocrine Society Clinical Practice Guidelines for Diagnosis and Treatment of Hyperprolactinemia