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< Chief complaint
>
A 47-year-old man with a progressive decrease
in libido and sexual activity for 2 months
< Case presentation
>
This 47-year-old
married man is a patient with essential hypertension for 2
years and had regular medical control with amlodipine besylate
5 mg QD. He had two children. Two months prior to admission,
he noted a progressive decrease in libido and frequency of
sexual activity. He almost totally lost libido axillary hair,
pubic hair, eyebrow and moustache. He visited an outpatient
department where bilateral atrophic testes were noted. He had
neither headache nor visual problems. Under the impression of
androgen deficiency, he was admitted for further management.
< Physical examination
>
Physical examination
revealed a 70 kg, 173 cm tall man with blood pressure 130/80
mmHg, respiratory rate 20/min, pulse rate 84/min and
temperature 37℃. The consciousness was clear, the conjunctivae
were pink, and the sclerae were anicteric. The pupils were
isocoric (3/3 mm) with prompt light reflex. The neck was
supple without goiter, lymphadenopathy or engorged jugular
veins. Chest, abdominal and extremity examinations were
normal. The areolae were hypopigmented, No gynecomastia,
galactorrhea, or purple striae was noted. The testes were
atrophic with size of 1.5×1.0 cm. The eyebrow, moustache,
axillary hair, and pubic hair were scanty. Neurological
examinations including visual fields, motion of eye balls and
hearing function were normal.
< Laboratory data
>
Table 1. Basal endocrine test level
|
hsTSH |
free T4
|
ACTH(A) |
Cortisol(A) |
ACTH(P) |
Cortisol(P) |
|
0.4- 4
μIU/mL
|
0.60-1.75
ng/dL |
10-65
pg/mL |
5-25
μg/dL |
10-65
pg/mL |
2.5-12.5
μg/dL |
|
2.98 |
0.37 |
9.9 |
1.4 |
8.0 |
＜ 1 |
|
hGH |
FSH |
LH |
Prolactin |
DHEA-SO4
|
Androstenedione |
|
0.06-5
ng/mL |
3.4-10
mIU/mL |
1.6-8.3
mIU/mL |
1.4-24.2
ng/mL |
4.6-15.4
μmol/L |
1.75-8.7
nM |
|
0.08 |
0.37 |
＜ 0.7 |
3938 |
＜ 0.81 |
＜
0.35 |
|
E2
|
P4 |
Testosterone |
MA |
TA |
|
73.4-367
pg/mL |
0.2-1.4
ng/mL |
10-50
ng/mL |
|
|
|
21.4 |
＜ 0.2 |
＜ 0.2 |
1：40(-) |
1：40(-) | **high
sensitivity thyroid-stimulating hormone＝hsTSH, free
thyroxine＝FT4, corticotropin＝ACTH, A＝8AM, P＝4PM, growth
hormone＝hGH, follicle-stimulating hormone＝FSH, luteinizing hormone＝LH, DHEA-SO4＝dehydroepiandrosterone sulfate, E2＝estradiol, P4＝ progesterone, MA＝microsomal
antibodies, TA＝thyroglobulin antibodies.
< Course and treatment
>
Biochemistry
studies and complete blood counts were within normal ranges. Baseline
serum hormone levels revealed hyperprolactinemia, hypogonadotropic
hypogonadism and panhypopituitarism. Skull films
showed an enlarged sellar turcica（Fig 1）. Prolactinoma was
suspected. Magnetic resonance imaging (MRI) demonstrated an
enlarged sellar turcica with a mass lesion(about 2.5
× 2 × 2cm) at the sellar and suprasellar region which invaded
to left cavernous sinus（Fig 2, 3, 4 &
5 ）.
The optic chiasm was elevated
and the posterior lobe of the pituitary gland was absent.
Pituitary macroadenoma was impressed. He received hormone
replacement therapy including thyroxin 100 μg QD, prednisolone
5- 2.5 mg B.I.D, and testosterone enanthate depot 125 mg per
month. Initially, bromocriptine 2.5 mg QD was prescribed for
reducing tumor size and prolactin level. The dose gradually
increased to 2.5 mg T.I.D. He could tolerate the mild nausea
and dizziness related to the medications. Follow-up prolactin
level decreased to 30 ng/mL. Surgical resection of the tumor
was suggested but he refused. He regularly followed up at our
hospital.
< Discussion
>
乳促素瘤（prolactinoma）是腦下腺腺瘤（pituitary
adenoma）中最常見的，約佔60％左右。乳促素瘤通常從腦下腺前葉的側翼（lateral
wings）長出，隨著時間漸漸充滿整個蝶鞍，甚至壓迫腦下腺前葉及後葉。腫瘤大小可以多變，從微腺瘤（microadenoma，直徑小於1公分）到巨大腺瘤（macroadenoma，直徑1公分以上），甚至往蝶鞍外侵犯都有可能，大部份在診斷時是微腺瘤。一般而言，乳促素瘤的生長是很慢的，甚至有些研究顯示大部分的微腺瘤是不會長大的。其發生率沒有性別上的差異。
女性以無月經（amenorrhea）及乳溢（galactorrhea）為主要表現，男性則以性慾降低（decreased
libido）和陽萎為主（impotence）。女性病患在診斷時通常腫瘤較小，可能是因為症狀較早出現，而男性因為起始症狀不明顯而常常延遲診斷，因此發現時腫瘤通常較大，就像我們的病人。
大部分的女性病人都會出現乳溢症狀，可以持續存在，也可以短暫或間歇性出現；少部份病人雖然血中乳促素很高卻沒有乳溢症狀，可能是因為同時缺乏性腺激素（gonadal
hormones）。90％的女性病人會有無月經、月經稀少、無排卵或是不孕，這些病人可以同時、之前或之後出現乳溢。造成性腺功能低下（hypogonadism）不是因為破壞促性腺激素分泌細胞（gonadotropin-secreting
cells），因為當血中乳促素濃度回到正常值後，月經週期也會恢復正常。雖然基礎的促性腺激素（gonadotropins）常常在正常範圍內，但是乳促素會抑制促性腺激素正常的脈動性分泌及促黃體生成素高峰（LH
surge），導致不排卵，也會抑制雌激素（estrogen）不分泌。因此這些病人是缺乏雌激素的，很容易會出現骨質疏鬆症。
過多的乳促素偶而會使得男性病人出現乳溢，然而，大部分卻是造成性腺功能低下。最初的症狀通常是性慾降低，因此常常被認為是精神上的問題，使得病人難以開口，也容易讓醫師失去警覺，造成診斷延遲，以致男性病人經常有較高的乳促素（乳促素大於200
ng/mL）及蝶鞍變大，甚至頭痛、視力不良或性腺功能低下。雖然血中睪固酮濃度很低，但是造成陽萎的原因不明，如果沒有矯正乳促素濃度，即使注射睪固酮也無法改善。許多情況都會造成血中乳促素增加，應該進一步鑑別診斷，包括一些生理性反應，如懷孕、哺乳、刺激乳頭、運動、壓力（低血糖）、睡眠、癲癇發作、新生兒時期；疾病，如脊柱疾病、下視丘及腦下腺柄疾病、原發性甲狀腺功能低下、慢性腎衰竭及嚴重肝疾病；還有一些藥物也會造成乳促素增加，如estrogen、dopamine
antagonists (phenothiazines, haloperidol, risperidone,
metoclopramide)、cimetidine、verapamil；臨床上尤其常見藥物造成乳促素增加，因此詢問病史時要小心藥物。
在診斷方面，除了典型的症狀外，就是測量血中乳促素濃度和影像檢查（包括頭部X光和核磁共振）。除了少數例外，當血中乳促素大於200
ng/mL，可以確定是乳促素瘤而且是巨大腺瘤；血中乳促素介於100到200
ng/mL，通常病人是乳促素瘤，可以是微腺瘤或巨大腺瘤；乳促素大於100
ng/mL的腺瘤通常可以在影像上清楚顯示；如果乳促素介於20至100
ng/mL之間，通常診斷較困難，此時需要依賴核磁共振檢查。
所有的病人都應該接受治療以防腫瘤長大、骨質疏鬆、及性腺功能低下。治療包括內科治療、手術切除及放射線治療。對於微腺瘤通常建議以內科治療為主，可以用dopamine
agonist，可以直接抑制乳促素分泌，包括bromocriptine及cabergoline，前者副作用較多，包括頭暈、噁心、嘔吐、姿勢性低血壓，建議從低劑量開始；後者較長效（一星期一到兩次）、較有效且副作用較少。對於巨大腺瘤一般建議手術治療，但是應該先使用內科治療，手術之後通常須輔以藥物治療甚至放射線治療。
為了能早期診斷，所以病人如果有乳溢、無月經、性慾減低、陽萎、不孕、蝶鞍變大、或懷疑腦下腺腫瘤時，都應該測乳促素濃度。
< References
>
- Bevan JS et al: dopamine agonists
and pituitary tumor shrinkage. Endocr Rev 1992;13:220.
- Colao A et al: Prolactinomas
resistant to standard dopamine agonists respond to chronic
cabergoline treatment. J Clin Endocrinol Metab 1997;82:876.
- Molitch ME: Diagnosis and treatment
of prolactinomas. Endocrinol Metab Clin North Am
1999;28:143.
- Verhelst J et al: Cabergoline in the
treatment of hyperprolactinemia: a study in 455 patients. J
Clin Endocrinol Metab 1999;84:2518.
- Vance ML et al: Treatment of prolactin-secreting
pituitary macroadenoma with the long-acting non-ergot
dopamine agonist CV 205-502. Ann Intern Med 1990;112:668.
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Case Discussion
繼續教育考題