Case Studies
Insidious Onset of Visual Disturbances in a Healthy
56-Year-Old Man
Michael Sealfon, PhD,1 Seth Franklin, MD2
(1Renton Technical College, Renton, WA, and 2Mercer Island Clinic of Medicine, Mercer Island, WA)
DOI: 10.1309/QDNQCF9JP22WK96E
Case History
Patient
56-year-old man
Chief Complaint
Double vision, increased light sensitivity, and
increased somnolence.
Principal Medical and Laboratory Findings
The NMI scan revealed a 1-cm pituitary
lesion (Image 1). A subsequently ordered
prolactin test yielded a value of 990 ng/
mL. The patient was immedately placed on a
successful therapeutic regime consisting of a
DOPA agonist. Within 3 weeks, his headaches
subsided and his vision returned to normal.
Medical History and Laboratory Findings
The patient is a white male in excellent
physical condition with no history of tobacco
or alcohol use. He had previously been treated
with both upper- and lower-body radiation
and CHOP chemotherapy for non-Hodgkin’s
lymphoma 30-years prior to this disorder
and has remained disease-free during this
period. His mother died at age 69 due to the
complications of sclerosing scleroderma and
his father succumbed to the complications of
severe Alzheimer’s disease at age 85.
Questions
1. Why did the primary clinical symptoms involve visual
disturbances?
2. Was increased somnolence an important symptom?
3. What is the patient’s most likely diagnosis?
4. What other laboratory tests should be ordered?
5. Why is a DOPA agonist a successful modality of therapy?
Possible Answers
1. The diagnosis is generally entertained on the basis of
visual difficulties arising from the compression of the optic nerve
by either a primary pituitary tumor or, more rarely, metastases
to the pituitary from primary breast or lung carcinomas. The
incidence is highest in breast cancer patients since the prolactin
(PRL)-rich environment in the pituitary is thought to enchance
the proliferation of breast tumor cells. The specific area of the
visual pathway at which compression by these tumors occurs is
at the optic chiasma.
The anatomy of this structure causes pressure on it to
produce a defect in the temporal visual field on both sides, a
condition called bitemporal hemianopia. Visual accuity can be
decreased in one or both eyes, pupillary light reaction can be
abnormal, and color vision may be affected.
Tumors which cause visual difficulty are likely to be macroadenomata greater than 10 mm in diameter; tumors less than
10 mm are microadenomata.
Some pituitary tumors secrete more than one hormone,
the most common combination being GH and prolactin.
2. The increased feeling of somnolence was a result of
increased levels of prolactin, which is produced in the anterior lobe of the pituitary gland. Prolactin is the principal
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Laboratory Tests
Chem 7
Glucose
Urea nitrogen
Creatinine
Sodium
Potassium
Chloride
CO2
Calcium
Phosphorus
FT4
TSH
Prolactin
Testosterone, total 97 mg/dL (70–125)
22 H mg/dL (9–20)
1.2 mg/dL (0.8–1.5)
143 mmol/L (137–145)
4.1 mmol/L (3.8–5.2)
104 mmol/L (98–107)
25 mmol/L (22–20)
9.3 mg/dL (8.4–10.2)
2.4 L mg/dL (2.5–4.5)
3.5 ug/dL (4.6–10.5)
6.5 uIU/mL (0.5–8.9)
990 H ng/mL (3.0–14.7)
<250 L ng/dL (260–1,000)
Complete Blood Count
WBC
RBC
HGB
HCT
MCV
MCH
PLT
Neut%
Lymph%
Mono%
Eos%
Baso%
Urinalysis (not performed)
6.1 x 109/L
3.80 L x 1012/L
11.4 L g/dL (14.0–17.0)
33.5 L% (41–49)
87.9 fL (80–98)
30.0 pg (26.7–33.7)
254 x 109/L (140–420)
74 (39–77)
14 (14–46)
10 (3–13)
2 (0–7)
0 (0–3)
Blood Pressure
115/70 mm
FT4, free thyroxine; TSH, thyroid-stimulating hormone; WBC, white blood cell count; RBC,
red blood cell count; HGB, hemoglobin; HCT, hematocrit; MCV, mean corpuscular volume;
MCH, mean corpuscular hemoglobin; PLT, platelet count.
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History of Present Illness
The patient was referred to his physician
following a 9-month period of deteriorating
vision and the recent onset of painful and
unremitting headaches. The previous summer,
the patient had experienced a sudden
onset of double vision which seemingly was
corrected with new eyeglasses prescribed by
his optometrist. Within 6 months, the double
vision had returned. A subsequent ocular field
examination was unremarkable, and a new
set of eyeglasses was subsequently ordered.
While awaiting the new eyeglasses, he began
to experience a decreased ability to tolerate
bright sunlight and a sudden increase in
somnolence as evidenced by the frequent need
to nap during daytime activities. When the new
eyeglasses arrived, they did not ameliorate any
of the ocular symptoms, and the patient, who
was a reference laboratory technical director,
was referred to an ophthamologist who
immediately ordered a nuclear magnetic image
(NMI) scan of the brain.
Case Studies
3. Most likely diagnosis: A prolactin-secreting pituitary
adenoma, though secondary tumor metastases to the posterior
pituitary must also be considered. Serum prolactin levels
should be measured in any patient with a suspected sellar
or suprasellar mass (normal reference range is <25 ng/mL).
Image 1_MRI scan demonstrating a pituitary adenoma.
Table 1_Medications Causing Hyperprolactinemia
Psychiatric medications
Anti-hypertensive medications
Hearburn-suppressant medications
Estrogens
Opiates
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hormone that controls the initiation and maintenance of
lactation in females. It has effects on the immune system
and is important in the control of osmolality and various
other metabolic events. It is secreted in a circadian cycle with
the highest levels being attained during sleep and a nadir
between 10 am and noon. Prolactin also acts at the level
of hypothalamus to inhibit the secretion of gonadotropinreleasing hormone (GnRH). Inhibition of GnRH results in
a decrease in the release of luteinizing hormone (LH) and
follicle-stimulating hormone (FSH), and a decrease in testicular function and synthesis of testosterone, and a halt in
spermatogenesis. Basal gonadotropin concentrations are low
in most patients with hyperprolactinemia; most studies suggest that PRL causes functional hypogonadism. Other pituitary hormone levels are usually normal, except in individuals
with very large tumors.
Circulating prolactin is heterogeneous in nature with
the most common monomeric form in healthy individuals
and in most patients with hyperprolactinemia. Higher molecular mass forms (ie, big prolactin [MW 60,000] or macroprolactin [MW 150,000]) sometimes predominate. Unlike
monomeric prolactin (MP), macroprolactin is considered
biologically inactive in vivo, but is retains immunoreactivity
and is detected, in various proportions, by all prolactin immunoassays. This immunoreactivity has a potential for prolactin misdiagnosis.
Case Studies
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If elevated, investigate the possibility of pharmacologic and
other factors prior to ordering extensive neuroimaging studies. Prolactin levels are increased by many physiologic and
pathologic factors as well as a wide variety of medications
(Table 1). Elevations from these stimuli rarely exceed 200 ng/
mL. Generally, a single elevated prolactin level may confirm the diagnosis. A serum prolactin level >200 ng/mL in
a patient with a macroadenoma greater than 10 mm in size
is diagnostic of a prolactinoma. Levels below that range in
a macroadenoma suggest hyperprolactinemia secondary to
hypothalamic compression. The degree of prolactin elevation
correlates fairly well with the size of the tumor.
Macroprolactinemic patients lack the classic signs and
symptoms of the hyperprolactinemic syndrome, but may
show nonspecific signs of hyperprolactinemia, making a differential diagnosis between an apparently benign condition
and that which requires surgical or therapeutic intervention
difficult.
Hyperprolactinemia exists in 20% to 40% of patients
with acromegaly; this is due either to the presence of a
mixed tumor or to interference with the normally active prolactin-inhibitory mechanisms (eg, interruption of
dopamine delivery). Another important cause of hyperprolactinemia is hypothryroidism. Thyrotropin-releasing
hormone (TRH) not only stimulates TSH secretion, but
also stimulates prolactin secretion.
With a prolactin level of 990 ng/mL combined with
a positive NM scan, the diagnosis of a prolactin-secreting
pituitary adenoma was the most likely diagnosis. Older studies have estimated the incidence of pituitary adenomas to be
about 200 cases per million. A recent study from Belgium
shows that pituitary adenomas are much more common than
previously believed (a 3- to 5-fold increase).
In a study from Liège, Belgium, the incidence is 94 per
100,000 with the male-to-female ratio of 2:3. The mean age
at the time of diagnosis is 40 years. In 42% of cases, the adenoma was >1 cm (macroadenoma).
4. It is important to evaluate all patients discovered to
have an abnormally elevated prolactin. Thyroid-function
tests (free thyroxine [FT4] and TSH) are always indicated
to rule out hypothyroidism. Since hyperprolactinemia can
be found in upwards of 40% of cases of acromegaly, it is
appropriate to measure insulin-like growth factor (ILF-1).
Other hormones that may be assayed include LH, FSH,
testrosterone, and/or estradiol. All patients should undergo
an MRI of the sella.
Routine screening and polyethylene glycol (PEG) pretreatment of hyperprolactinemic sera to remove the benign
macroprolactin interfenents has been recently recommended.
Such pretreatment can reduce the need for more costly procedures (ie, NMI and dopamine agonist prescriptions).
5. Prolactinomas are most often treated with bromocriptine or, more recently, cabergoline, which are DOPA stimulants and are negative-feedback inhibitors of PRL production.
Either of these dopamine agonists are followed by serial NMI
imaging to detect changes in tumor size. Treatment, where
the tumor is large, can be with radiation therapy or surgery,
and patients generally respond well. Efforts have been made to
use a progesterone antagonist for the treatment of prolactinomas, but so far have not proved successful. LM
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Case Studies
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