Prolactinoma
Prolactinoma
郝 立 智 醫 師
郝 立 智 醫 師
永康榮民醫院新陳代謝科
永康榮民醫院新陳代謝科

NEJM, Vol 349:2035-2041, Nov. 20, 2003, No. 21.

HLJ
Outline
Outline
•
Case Presentation
Case Presentation
•
The Clinical Problem
The Clinical Problem
–
Clinical Presentation
Clinical Presentation
–
Causes of Hyperprolactinemia
Causes of Hyperprolactinemia


•
Strategies and Evidence
Strategies and Evidence
–

Diagnostic Studies
Diagnostic Studies
–
Therapy
Therapy


Microadenomas Macroadenomas Hypogonadism
Microadenomas Macroadenomas Hypogonadism


•
Areas of Uncertainty
Areas of Uncertainty


•
Guidelines
Guidelines
•
Conclusions and Recommendations
Conclusions and Recommendations

HLJ
Case Presentation
Case Presentation
•
A 22-year-old woman who wants to become pregnant has
A 22-year-old woman who wants to become pregnant has
had

had
no menses
no menses
since she discontinued the use of an oral
since she discontinued the use of an oral
contraceptive one year ago, and recently,
contraceptive one year ago, and recently,
galactorrhea
galactorrhea


developed.
developed.
•
She takes no medications and has had no headaches, visual
She takes no medications and has had no headaches, visual
loss, dyspareunia, or decreased libido.
loss, dyspareunia, or decreased libido.
•
P.E. shows no abnormalities, except for the
P.E. shows no abnormalities, except for the
bilateral breast
bilateral breast
discharge
discharge
.
.
•
A test for serum HCG is negative, the thyrotropin level is
A test for serum HCG is negative, the thyrotropin level is

normal, and the serum
normal, and the serum
prolactin
prolactin
level is
level is
95 µg /l.
95 µg /l.
•
MRI reveals a mass,
MRI reveals a mass,
3 mm
3 mm
in diameter, in the anterior lobe
in diameter, in the anterior lobe
of the pituitary.
of the pituitary.
•
How should she be treated?
How should she be treated?



HLJ
The Clinical Problem
The Clinical Problem
•
Prolactin-secreting tumors
Prolactin-secreting tumors
are benign neoplasms that

are benign neoplasms that
account for about
account for about
40 %
40 %
of all pituitary tumors.
of all pituitary tumors.
•
Over
Over
90 %
90 %
are small, intrasellar tumors that rarely
are small, intrasellar tumors that rarely
increase in size.
increase in size.
•
The primary action of prolactin is to stimulate lactation,
The primary action of prolactin is to stimulate lactation,
but it is the effect of prolactin on gonadal function that
but it is the effect of prolactin on gonadal function that
warrants clinical attention.
warrants clinical attention.
•
Hypersecretion of prolactin leads to infertility and
Hypersecretion of prolactin leads to infertility and
gonadal dysfunction by
gonadal dysfunction by
interrupting secretion of
interrupting secretion of

gonadotropin-releasing hormone
gonadotropin-releasing hormone
, inhibiting the release
, inhibiting the release
of
of
LH and FSH
LH and FSH
, and
, and
impairing gonadal steroidogenesis
impairing gonadal steroidogenesis
.
.

HLJ
Prolactin inhibits oestrogen synthesis in the ovary
Prolactin inhibits oestrogen synthesis in the ovary
•
In
In
20%
20%
of cases of secondary amenorrhoea,
of cases of secondary amenorrhoea,
hyperprolactinaemia
hyperprolactinaemia
prevents ovulation by impairing normal
prevents ovulation by impairing normal
follicular development, but little is known of the

follicular development, but little is known of the
biochemical basis for this effect.
biochemical basis for this effect.
•
Bromocriptine
Bromocriptine
can restore follicular growth and ovulation
can restore follicular growth and ovulation
by inhibiting the release of prolactin from the pituitary.
by inhibiting the release of prolactin from the pituitary.
•
The
The
suckling stimulus
suckling stimulus
causes an increase in prolactin levels,
causes an increase in prolactin levels,
and ovarian follicles fail to develop fully, thus
and ovarian follicles fail to develop fully, thus
inducing an
inducing an
anovulatory state
anovulatory state
throughout lactation in many mammals.
throughout lactation in many mammals.
•
We report here experiments with cultured granulosa cells
We report here experiments with cultured granulosa cells
which suggest that this
which suggest that this

contraceptive action of prolactin
contraceptive action of prolactin
is
is
due to its ability to
due to its ability to
interfere with the action of FSH on the
interfere with the action of FSH on the
synthesis of oestrogen
synthesis of oestrogen
.
.
Nature. 1981 Apr 16;290(5807):600-2.

HLJ

HLJ
Clinical Presentation (1)
Clinical Presentation (1)
•
The most common symptoms of hyperprolactinemia in
The most common symptoms of hyperprolactinemia in
premenopausal women are
premenopausal women are
amenorrhea and infertility
amenorrhea and infertility
.
.
•
Galactorrhea

Galactorrhea
occurs in about 80 % of such women, and
occurs in about 80 % of such women, and
some women with prolactinomas have infrequent
some women with prolactinomas have infrequent
menstrual flow (oligomenorrhea) or regular menses.
menstrual flow (oligomenorrhea) or regular menses.
•
Hyperprolactinemia is often detected after discontinuation
Hyperprolactinemia is often detected after discontinuation
of an oral contraceptive, but there is
of an oral contraceptive, but there is
no apparent relation
no apparent relation


between the use of oral contraceptives and the formation
between the use of oral contraceptives and the formation
of prolactinomas.
of prolactinomas.
•
The majority of prolactinomas
The majority of prolactinomas
in women
in women
are small at the
are small at the
diagnosis, and headaches and neurologic deficits are rare.
diagnosis, and headaches and neurologic deficits are rare.


HLJ
Clinical Presentation (2)
Clinical Presentation (2)
•
In contrast, prolactinomas
In contrast, prolactinomas
in men
in men
typically tend to be large
typically tend to be large
at the time of diagnosis and may cause cranial-nerve
at the time of diagnosis and may cause cranial-nerve
dysfunction, visual loss, and hypopituitarism.
dysfunction, visual loss, and hypopituitarism.
•
In men, hyperprolactinemia leads to impotence, infertility,
In men, hyperprolactinemia leads to impotence, infertility,
and decreased libido, but these are rarely the initial
and decreased libido, but these are rarely the initial
symptoms; galactorrhea and gynecomastia are uncommon.
symptoms; galactorrhea and gynecomastia are uncommon.
•
In both sexes, long-standing hyperprolactinemia leads to
In both sexes, long-standing hyperprolactinemia leads to
low bone density in the spine
low bone density in the spine
.
.
•
After prolactin has returned to the normal range,

After prolactin has returned to the normal range,
bone
bone
density will increase but does not reach normal values.
density will increase but does not reach normal values.

HLJ
Prolactin-secreting tumors and
Prolactin-secreting tumors and
hypogonadism in 22 men
hypogonadism in 22 men
•
We studied 22 men with prolactin-secreting pituitary tumors and
We studied 22 men with prolactin-secreting pituitary tumors and
hypogonadism. Twenty complained of impotence, nine had visual
hypogonadism. Twenty complained of impotence, nine had visual
impairment, and three experienced galactorrhea. None of the 17 p'ts
impairment, and three experienced galactorrhea. None of the 17 p'ts
undergoing operation or radiotherapy, or both, were subsequently
undergoing operation or radiotherapy, or both, were subsequently
normoprolactinemic. In all 13 p'ts treated with bromocryptine,
normoprolactinemic. In all 13 p'ts treated with bromocryptine,
major clinical improvement was associated with a decrease in serum
major clinical improvement was associated with a decrease in serum
prolactin levels and in nine with an increase in serum testosterone.
prolactin levels and in nine with an increase in serum testosterone.
•
Two p'ts receiving testosterone replacement therapy showed
Two p'ts receiving testosterone replacement therapy showed
improved potency only after bromocryptine was administered.

improved potency only after bromocryptine was administered.
•
The results indicate that
The results indicate that
hyperprolactinemia frequently induces
hyperprolactinemia frequently induces
hypogonadism in men
hypogonadism in men
, that bromocryptine ameliorates symptoms of
, that bromocryptine ameliorates symptoms of
disease previously unchanged by operation or radiotherapy, and
disease previously unchanged by operation or radiotherapy, and
the
the
impotence observed may not be solely the result of hypogonadism.
impotence observed may not be solely the result of hypogonadism.


N Engl J Med 1978;299:847-852.

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Bone Marker and Bone Density Responses to Dopamine
Bone Marker and Bone Density Responses to Dopamine
Agonist Therapy in Hyperprolactinemic Males
Agonist Therapy in Hyperprolactinemic Males


•
The aim of this prospective study was to evaluate the bone mineral
The aim of this prospective study was to evaluate the bone mineral

density (BMD) at lumbar spine and femoral neck levels and
density (BMD) at lumbar spine and femoral neck levels and
biochemical parameters of bone turnover in 20 consecutive
biochemical parameters of bone turnover in 20 consecutive
hyperprolactinemic males before and after an 18-month treatment
hyperprolactinemic males before and after an 18-month treatment
with different dopamine agonists.
with different dopamine agonists.
•
Six p'ts received
Six p'ts received
bromocriptine
bromocriptine
at a dose of 2.5–10 mg/day;
at a dose of 2.5–10 mg/day;
•
7 p'ts received
7 p'ts received
quinagolide
quinagolide
at a dose of 0.075–0.3 mg/day;
at a dose of 0.075–0.3 mg/day;
•
7 p'ts received
7 p'ts received
cabergoline
cabergoline
at a dose of 0.5–1.5 mg/wk.
at a dose of 0.5–1.5 mg/wk.
•

BMD, serum PRL, testosterone, dihydrotestosterone, and
BMD, serum PRL, testosterone, dihydrotestosterone, and
osteocalcin (OC), and urinary cross-linked
osteocalcin (OC), and urinary cross-linked
N
N
-telopeptides of type I
-telopeptides of type I
collagen (Ntx) levels were measured before and every 6 months
collagen (Ntx) levels were measured before and every 6 months
during treatment.
during treatment.
J Clin Endocrinol Metab 1998;83:807-813

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•
At study entry, BMD values were lower in p'ts than controls at both
At study entry, BMD values were lower in p'ts than controls at both
lumbar spine (0.82 ± 0.03
lumbar spine (0.82 ± 0.03
vs.
vs.
1.18 ± 0.01 g/cm2;
1.18 ± 0.01 g/cm2;
P
P
< 0.001) and
< 0.001) and
femoral neck (0.85 ± 0.02
femoral neck (0.85 ± 0.02

vs.
vs.
0.92 ± 0.02 g/cm2;
0.92 ± 0.02 g/cm2;
P
P
< 0.05) levels.
< 0.05) levels.
Osteopenia or osteoporosis was diagnosed in 16 p'ts at the lumbar
Osteopenia or osteoporosis was diagnosed in 16 p'ts at the lumbar
spine and in 6 of them at the femoral neck level.
spine and in 6 of them at the femoral neck level.
•
A significant inverse correlation was found between lumbar spine
A significant inverse correlation was found between lumbar spine
and femoral neck BMD values and both PRL levels and disease
and femoral neck BMD values and both PRL levels and disease
duration (
duration (
P
P
< 0.01).
< 0.01).
•
In the 20 p'ts, serum OC levels were significantly lower (2.1 ± 0.1
In the 20 p'ts, serum OC levels were significantly lower (2.1 ± 0.1
vs.
vs.
9.3 ± 2.4 µg/L;
9.3 ± 2.4 µg/L;

P
P
< 0.01), whereas Ntx levels were significantly
< 0.01), whereas Ntx levels were significantly
higher (157.8 ± 1.1
higher (157.8 ± 1.1
vs.
vs.
96.4 ± 7.4 nmol bone collagen
96.4 ± 7.4 nmol bone collagen
equivalent/mmol creatinine;
equivalent/mmol creatinine;
P
P
< 0.001) than control values.
< 0.001) than control values.
•
A significant inverse correlation was found between serum PRL and
A significant inverse correlation was found between serum PRL and
OC (
OC (
P
P
< 0.01), but not Ntx, levels.
< 0.01), but not Ntx, levels.
J Clin Endocrinol Metab 1998;83:807-813

HLJ
•
After 18 months of treatment, serum PRL levels were suppressed,

After 18 months of treatment, serum PRL levels were suppressed,
and gonadal function was restored in all 20 p'ts, as shown by the
and gonadal function was restored in all 20 p'ts, as shown by the
normalization of serum T (from 2.2 ± 0.2 to 5.0 ± 0.2 µg/L) and
normalization of serum T (from 2.2 ± 0.2 to 5.0 ± 0.2 µg/L) and
dihydrotestosterone (0.3 ± 0.02
dihydrotestosterone (0.3 ± 0.02
vs.
vs.
0.5 ± 0.01 nmol/L) levels,
0.5 ± 0.01 nmol/L) levels,
without any significant difference among groups.
without any significant difference among groups.
•
A progressive significant increase in serum OC levels together
A progressive significant increase in serum OC levels together
with a significant decrease in Ntx levels were observed after 6,
with a significant decrease in Ntx levels were observed after 6,
12, and 18 months of treatment in the 3 groups of p'ts.
12, and 18 months of treatment in the 3 groups of p'ts.
•
A slight, although significant,
A slight, although significant,
increase in BMD values
increase in BMD values
was
was
recorded in all p'ts after 18 months of
recorded in all p'ts after 18 months of
bromocriptine,

bromocriptine,
quinagolide, and cabergoline
quinagolide, and cabergoline
treatment,
treatment,
serum OC levels were
serum OC levels were
normalized after treatment
normalized after treatment
, whereas
, whereas
neither urinary Ntx levels
neither urinary Ntx levels
nor BMD values were normalized
nor BMD values were normalized
by 18 months of treatment
by 18 months of treatment
with dopaminergic agents.
with dopaminergic agents.
J Clin Endocrinol Metab 1998;83:807-813

HLJ
•
In conclusion, treatment with
In conclusion, treatment with
bromocriptine, quinagolide, and
bromocriptine, quinagolide, and
cabergoline
cabergoline
for 18 months, although successfull in suppressing

for 18 months, although successfull in suppressing
serum PRL levels and restoring gonadal function, was
serum PRL levels and restoring gonadal function, was
unable to
unable to
restore lumbar spine and femoral neck BMD and normalize Ntx
restore lumbar spine and femoral neck BMD and normalize Ntx
levels.
levels.


•
However, BMD was slightly increased during treatment, suggesting
However, BMD was slightly increased during treatment, suggesting
that
that
additional bone loss was prevented after treatment of
additional bone loss was prevented after treatment of
hyperprolactinemia.
hyperprolactinemia.
J Clin Endocrinol Metab 1998;83:807-813

HLJ
Causes of Hyperprolactinemia (1)
Causes of Hyperprolactinemia (1)
•
The secretion and release of prolactin are mediated by
The secretion and release of prolactin are mediated by
dopamine
dopamine

, and any process that disrupts dopamine
, and any process that disrupts dopamine
secretion or interferes with the delivery of dopamine to
secretion or interferes with the delivery of dopamine to
the portal vessels may cause hyperprolactinemia.
the portal vessels may cause hyperprolactinemia.
•
Normal prolactin levels in women and men are below 25
Normal prolactin levels in women and men are below 25
µg/l and 20 µg/l, respectively. There is a
µg/l and 20 µg/l, respectively. There is a
10-fold
10-fold


increase in prolactin during
increase in prolactin during
pregnancy
pregnancy
, and levels rise
, and levels rise
after
after
exercise, meals, and stimulation of the chest wall.
exercise, meals, and stimulation of the chest wall.
•
Physical and psychological stress
Physical and psychological stress
increases the secretion
increases the secretion

of prolactin, but rarely exceeds 40 µg/l.
of prolactin, but rarely exceeds 40 µg/l.
•
Breast examination
Breast examination
is infrequently associated with
is infrequently associated with
elevation of the prolactin level.
elevation of the prolactin level.

HLJ
Causes of Hyperprolactinemia (2)
Causes of Hyperprolactinemia (2)
•
Metoclopramide, phenothiazines, and butyrophenones
Metoclopramide, phenothiazines, and butyrophenones


antagonize lactotroph dopamine receptors, leading to
antagonize lactotroph dopamine receptors, leading to
prolactin levels that exceed 100 µg /l.
prolactin levels that exceed 100 µg /l.
•
Risperidone
Risperidone
causes a similar elevation, and
causes a similar elevation, and
MAOIs
MAOIs
and

and
TCAs
TCAs
raise prolactin levels through effects on the delivery
raise prolactin levels through effects on the delivery
of dopamine to the portal vessels.
of dopamine to the portal vessels.
•
Serotonin-reuptake inhibitors
Serotonin-reuptake inhibitors
may cause
may cause
hyperprolactinemia, but the prolactin levels rarely exceed
hyperprolactinemia, but the prolactin levels rarely exceed
the normal range.
the normal range.
•
Nearly
Nearly
10 %
10 %
of p'ts taking
of p'ts taking
verapamil
verapamil
have elevated
have elevated
prolactin levels, but other CCBs are not associated with
prolactin levels, but other CCBs are not associated with
hyperprolactinemia.

hyperprolactinemia.

HLJ
The effects of olanzapine, risperidone, and haloperidol on
The effects of olanzapine, risperidone, and haloperidol on
plasma prolactin levels in p’ts with schizophrenia.
plasma prolactin levels in p’ts with schizophrenia.
•
BACKGROUND:
BACKGROUND:
There is relatively little comparative
There is relatively little comparative
information on elevations in plasma prolactin level (PRL)
information on elevations in plasma prolactin level (PRL)
with conventional versus novel antipsychotic agents.
with conventional versus novel antipsychotic agents.
•
OBJECTIVE:
OBJECTIVE:
This paper examines the comparative
This paper examines the comparative
effects on PRL of olanzapine, risperidone, and haloperidol
effects on PRL of olanzapine, risperidone, and haloperidol
based on data from 3 multicenter, double-blind,
based on data from 3 multicenter, double-blind,
randomized clinical trials. Magnitude of response, dose
randomized clinical trials. Magnitude of response, dose
dependency, time course, effects of sex and age, and
dependency, time course, effects of sex and age, and
response to switching from haloperidol to olanzapine are

response to switching from haloperidol to olanzapine are
assessed.
assessed.
Clin Ther 2000;22:1085-1096

HLJ
•
METHODS:
METHODS:
The effects of olanzapine, risperidone, and haloperidol on
The effects of olanzapine, risperidone, and haloperidol on
PRL were assessed in schizophrenia or related psychoses participating in
PRL were assessed in schizophrenia or related psychoses participating in
3 double-blind clinical trials: (1) a 6-wk acute trial comparing olanzapine
3 double-blind clinical trials: (1) a 6-wk acute trial comparing olanzapine
5 to 20 mg/d (n = 1,336) and haloperidol 5 to 20 mg/d (n = 660), with a
5 to 20 mg/d (n = 1,336) and haloperidol 5 to 20 mg/d (n = 660), with a
1-year, open-label olanzapine extension for responders; (2) a 54-wk
1-year, open-label olanzapine extension for responders; (2) a 54-wk
study comparing olanzapine 5 to 20 mg/d (n = 21), risperidone 4 to 10
study comparing olanzapine 5 to 20 mg/d (n = 21), risperidone 4 to 10
mg/d (n = 21), and haloperidol 5 to 20 mg/d (n = 23) in early illness; and
mg/d (n = 21), and haloperidol 5 to 20 mg/d (n = 23) in early illness; and
(3) a 28-wk study comparing olanzapine 10 to 20 mg/d (n = 172) and
(3) a 28-wk study comparing olanzapine 10 to 20 mg/d (n = 172) and
risperidone 4 to 12 mg/d (n = 167).
risperidone 4 to 12 mg/d (n = 167).
•
RESULTS:
RESULTS:

PRL elevations were significantly greater with
PRL elevations were significantly greater with
risperidone
risperidone


than with either olanzapine or haloperidol in study 2. and significantly
than with either olanzapine or haloperidol in study 2. and significantly
greater than with olanzapine in study 3 (all, P < 0.001). PRL elevations
greater than with olanzapine in study 3 (all, P < 0.001). PRL elevations
were significantly greater with
were significantly greater with
haloperidol
haloperidol
than with olanzapine in study
than with olanzapine in study
1 (P < 0.001 ). A dose-response relationship was not consistently
1 (P < 0.001 ). A dose-response relationship was not consistently
confirmed with any of the drug treatments. Risperidone-associated PRL
confirmed with any of the drug treatments. Risperidone-associated PRL
elevations peaked relatively early in treatment. In haloperidol- and
elevations peaked relatively early in treatment. In haloperidol- and
risperidone-treated p'ts, the mean change in PRL was greater in women
risperidone-treated p'ts, the mean change in PRL was greater in women
than in men. PRL decreased significantly when treatment was switched
than in men. PRL decreased significantly when treatment was switched
from haloperidol to olanzapine.
from haloperidol to olanzapine.
Clin Ther 2000;22:1085-1096


HLJ
•
CONCLUSIONS:
CONCLUSIONS:


1.
1.
This side-by-side analysis of 3 independent studies suggests
This side-by-side analysis of 3 independent studies suggests
that with the 3 antipsychotic drugs studied, PRL is elevated
that with the 3 antipsychotic drugs studied, PRL is elevated
moderately by olanzapine (mean change, 1-4 ng/mL),
moderately by olanzapine (mean change, 1-4 ng/mL),
intermediately by haloperidol (mean change, approximately 17
intermediately by haloperidol (mean change, approximately 17
ng/mL), and strongly by
ng/mL), and strongly by
risperidone
risperidone
(mean change, 45-80
(mean change, 45-80
ng/mL).
ng/mL).
2.
2.
No consistent dose-response relationship
No consistent dose-response relationship
was observed, and
was observed, and

the time course and sex-dependency of the response differed
the time course and sex-dependency of the response differed
between the 3 agents.
between the 3 agents.
3.
3.
P'ts with haloperidol-induced hyperprolactinemia may benefit
P'ts with haloperidol-induced hyperprolactinemia may benefit
from a switch to
from a switch to
olanzapine
olanzapine
.
.
4.
4.
Long-term studies examining the health consequences of
Long-term studies examining the health consequences of
chronic hyperprolactinemia
chronic hyperprolactinemia
during antipsychotic treatment are
during antipsychotic treatment are
needed
needed
Clin Ther 2000;22:1085-1096

HLJ
Causes of Hyperprolactinemia (3)
Causes of Hyperprolactinemia (3)
•

Less commonly used antihypertensive agents that are
Less commonly used antihypertensive agents that are
associated with hyperprolactinemia include
associated with hyperprolactinemia include
reserpine and
reserpine and
methyldopa
methyldopa
.
.
•
Prolactin levels may also be mildly elevated after the
Prolactin levels may also be mildly elevated after the
administration of
administration of
estrogen
estrogen
.
.
•
The magnitude of
The magnitude of
medication-induced elevations
medication-induced elevations
in the
in the
prolactin level is variable, and the level
prolactin level is variable, and the level
returns to normal
returns to normal

within days
within days
after the cessation of therapy.
after the cessation of therapy.
•
Medication-induced hyperprolactinemia is associated with
Medication-induced hyperprolactinemia is associated with
levels of prolactin in the range of
levels of prolactin in the range of
25 to 100 µg /l.
25 to 100 µg /l.

HLJ
Effects of methyldopa on prolactin and GH
Effects of methyldopa on prolactin and GH
•
The effects of administration of methyldopa on serum prolactin and
The effects of administration of methyldopa on serum prolactin and
GH concentrations in hypertensive p'ts were studied.
GH concentrations in hypertensive p'ts were studied.
•
Single doses of methyldopa (750 or 1000 mg) significantly
Single doses of methyldopa (750 or 1000 mg) significantly
increased serum prolactin levels, peak concentrations occurring
increased serum prolactin levels, peak concentrations occurring
four
four
to six hours
to six hours
after drug administrations.

after drug administrations.
•
Long-term methyldopa treatment was associated with
Long-term methyldopa treatment was associated with
threefold to
threefold to
fourfold increases in basal prolactin levels
fourfold increases in basal prolactin levels
compared with those in
compared with those in
normal subjects. In p'ts treated with methyldopa for two to three
normal subjects. In p'ts treated with methyldopa for two to three
wks the GH response to insulin hypoglycaemia was significantly
wks the GH response to insulin hypoglycaemia was significantly
greater than in normal subjects and untreated hypertensive p'ts.
greater than in normal subjects and untreated hypertensive p'ts.
•
In contrast, p'ts treated for prolonged periods (mean 13-4 months)
In contrast, p'ts treated for prolonged periods (mean 13-4 months)
had a GH reponse indistinguishable from normal.
had a GH reponse indistinguishable from normal.
Br Med J 1976;1:1186-1188.

HLJ
Augmentation of prolactin secretion by
Augmentation of prolactin secretion by
estrogen in hypogonadal women
estrogen in hypogonadal women
•
The effect of estrogen on PRL release and gonadotropin

The effect of estrogen on PRL release and gonadotropin
suppression was assessed in six experiments performed on four
suppression was assessed in six experiments performed on four
hypogonadal women.
hypogonadal women.
•
Ethinyl estradiol at a dose of 1 ug/kg/day induced a significant
Ethinyl estradiol at a dose of 1 ug/kg/day induced a significant
elevation of serum PRL levels within the 1st wk of treatment.
elevation of serum PRL levels within the 1st wk of treatment.
There was a further rise until a plateau was reached in about 3-4
There was a further rise until a plateau was reached in about 3-4
wk to levels of more than 3 times the initial concentration. This
wk to levels of more than 3 times the initial concentration. This
was accompanied by a pattern of increased episodic fluctuation.
was accompanied by a pattern of increased episodic fluctuation.
•
The corresponding serum LH and FSH fell progressively during
The corresponding serum LH and FSH fell progressively during
the study period.
the study period.
•
These data indicate that a
These data indicate that a
positive feedback relationship between
positive feedback relationship between
estrogen and PRL release
estrogen and PRL release
exists in humans.
exists in humans.

J Clin Invest 1974;53:652-655.

HLJ
Causes of Hyperprolactinemia (4)
Causes of Hyperprolactinemia (4)
•
Craniopharyngioma
Craniopharyngioma
,
,
acromegaly
acromegaly
,
,
granulomatous
granulomatous
infiltration of the hypothalamus
infiltration of the hypothalamus
,
,
severe head trauma
severe head trauma
, and
, and
large nonfunctioning pituitary tumors
large nonfunctioning pituitary tumors
may also lead to
may also lead to
hyperprolactinemia.
hyperprolactinemia.

•
In p'ts with acromegaly, prolactin may be secreted along
In p'ts with acromegaly, prolactin may be secreted along
with GH. The development of
with GH. The development of
large nonfunctioning
large nonfunctioning
pituitary tumors
pituitary tumors
can compress the pituitary stalk and lead
can compress the pituitary stalk and lead
to prolactin levels in the range of
to prolactin levels in the range of
25 to 200 µg/l
25 to 200 µg/l
, with
, with
increases to levels of less than 100 µg/l in most cases.
increases to levels of less than 100 µg/l in most cases.
•
In some p'ts with
In some p'ts with
primary hypothyroidism
primary hypothyroidism
, mild
, mild
hyperprolactinemia develops owing to the increased
hyperprolactinemia develops owing to the increased
synthesis of
synthesis of

TRH.
TRH.


•
Prolactin levels are elevated in
Prolactin levels are elevated in
chronic renal failure
chronic renal failure


because of decreased clearance of the hormone.
because of decreased clearance of the hormone.
Br Med J 1976;1:1186-1188.

HLJ
Causes of Hyperprolactinemia (5)
Causes of Hyperprolactinemia (5)
•
When no cause of hyperprolactinemia can be identified, the
When no cause of hyperprolactinemia can be identified, the
diagnosis is
diagnosis is
idiopathic hyperprolactinemia
idiopathic hyperprolactinemia
.
.
•
A prolactinoma may be present but may be too small to be
A prolactinoma may be present but may be too small to be

detected radiographically.
detected radiographically.
•
In
In
one third
one third
of p'ts with idiopathic hyperprolactinemia, the
of p'ts with idiopathic hyperprolactinemia, the
level of prolactin later returns to the normal range, and in
level of prolactin later returns to the normal range, and in
nearly half
nearly half
, it remains unchanged.
, it remains unchanged.
•
In one study, only
In one study, only
10 %
10 %
of p'ts with idiopathic
of p'ts with idiopathic
hyperprolactinemia had radiographic evidence of a pituitary
hyperprolactinemia had radiographic evidence of a pituitary
tumor during a follow-up period of
tumor during a follow-up period of
six years
six years
.
.


HLJ
Clinical history and outcome of 59 p'ts with
Clinical history and outcome of 59 p'ts with
idiopathic hyperprolactinemia
idiopathic hyperprolactinemia
•
OBJECTIVE:
OBJECTIVE:
To investigate the clinical course of
To investigate the clinical course of
hyperprolactinemia without demonstrable cause.
hyperprolactinemia without demonstrable cause.
•
DESIGN:
DESIGN:
Prospective study of all p'ts with idiopathic
Prospective study of all p'ts with idiopathic
hyperprolactinemia first seen between 1974 and 1985.
hyperprolactinemia first seen between 1974 and 1985.
•
SETTING:
SETTING:
Outp't Department of University Hospital.
Outp't Department of University Hospital.
•
P'ts:
P'ts:
Fifty-nine p'ts followed for 6 to 190 months (median
Fifty-nine p'ts followed for 6 to 190 months (median

78 months). Medical treatment given only in case of
78 months). Medical treatment given only in case of
anovulatory infertility or hypogonadism.
anovulatory infertility or hypogonadism.
•
OUTCOME MEASURES:
OUTCOME MEASURES:
Development of pituitary
Development of pituitary
(micro)prolactinoma, PRL levels, and clinical signs of
(micro)prolactinoma, PRL levels, and clinical signs of
menstrual dysfunction.
menstrual dysfunction.
Fertil Steril 1992;58:72-77.

HLJ
•
RESULTS:
RESULTS:


•
With exception of one woman in whom it probably had
With exception of one woman in whom it probably had
been missed by hypocycloidal tomography, no
been missed by hypocycloidal tomography, no
demonstrable prolactinoma developed.
demonstrable prolactinoma developed.
•
Prolactin levels rose in two p'ts, one using oral

Prolactin levels rose in two p'ts, one using oral
contraceptives and the other with prolactinoma.
contraceptives and the other with prolactinoma.
•
At the end of follow-up, 15 of 16 p'ts using a
At the end of follow-up, 15 of 16 p'ts using a
dopaminergic drug had a normal cycle; 13 had normal
dopaminergic drug had a normal cycle; 13 had normal
final PRL levels. From the 43 p'ts off medication, 28
final PRL levels. From the 43 p'ts off medication, 28
(66%) had normal PRL levels and 23 (54%) had a normal
(66%) had normal PRL levels and 23 (54%) had a normal
cycle.
cycle.
•
There were
There were
no significant differences
no significant differences
between women
between women
who had and had not been pregnant.
who had and had not been pregnant.
•
Dopaminergic medication had
Dopaminergic medication had
no appreciable influence
no appreciable influence



on the course of the disease.
on the course of the disease.
Fertil Steril 1992;58:72-77.