Thymoma associated with syndrome of inappropriate antidiuretic hormone secretion and myasthenia gravis.

Abstract

We describe the association of malignant thymoma with the syndrome of inappropriate antidiuretic hormone secretion and myasthenia gravis. Hyponatremia has not been reported associated with those tumors and our case should alert physicians about the potential for a life-threatening complication.

Full text

Page 1

278
March 1998 • SOUTHERN MEDICAL JOURNAL • Vol. 91, No. 3
T HE SYNDROME of inappropriate antidiuretic
hormone (SIADH) secretion has been associ-
ated with three classes of disorders—carcino-
mas, pulmonary, and central nervous system
abnormalities. The hyponatremia is due to
abnormal water metabolism. There is high
urine osmolality out of proportion to serum
osmolality and high urine sodium concentra-
tions. A diagnosis of SIADH may be made after
excluding other reasons for decreased diluting
capacity of the renal tubules, including renal,
pituitary, adrenal, thyroid, cardiac, or hepatic
diseases. The presence of non-osmotic stimuli
for ADH release, such as hemodynamic
derangements caused by hypotension, nausea,
or drugs must be ruled out. The patients have
had mental status changes, confusion, lethargy,
seizures, psychosis, coma, or even death due to
water intoxication of neuronal cells.1,2
We saw a patient with myasthenia gravis, thy-
moma, and hyponatremia. Although thy-
moma is listed as a disorder associated with
SIADH,2-4a literature review did not reveal a
study of this particular abnormality. We pre-
sent the following unique clinical case.
CASE REPORT
Our patient was a 77-year-old white woman who had a 1-
month history of right shoulder and neck pain. More
recently, she had anterior chest pain and discovered a
fixed lump between her right breast and sternum. She
complained of increasing fatigue, difficulty walking, and
problems with her speech. She denied fever, chills, sweats,
weight loss, or shortness of breath. The patient had no sig-
nificant medical history. She denied taking any medica-
tions or having drug allergies and had no history of
tobacco or alcohol use.
On initial examination, the patient was noted to have a
3 cm x 4 cm fixed mass between her right breast and ster-
num. She had no lymphadenopathy, her lungs were clear,
and there were no abdominal masses palpated. The patient
exhibited proximal muscle weakness in all four extremities
but had no muscle tenderness. She had no ptosis.
Laboratory tests were remarkable for sodium 125
mEq/L and lactate dehydrogenase 272 U/L. A chest radi-
ograph revealed large lobulated retrosternal densities and
ill-defined margins of the right 5th rib. A chest computed
tomography (CT) scan revealed two mediastinal masses
with distinct imaging characteristics—a lobulated low-den-
sity mass originating in the anterior mediastinum and
extending to the anterior chest wall and a second lesion in
the middle mediastinum that appeared vascular and
enhanced similarly to thyroid tissue. The thyroid scan was
normal. Bone scan showed increased uptake in the upper-
third of the sternum. Mammogram and CT of the head
were negative. An electromyogram revealed the presence
of an inflammatory myopathy.
With the above findings and an elevated creatine phos-
phokinase, her condition was most consistent with
polymyositis. The absence of muscle pain prompted a
search for other disorders and a high anti-acetylcholine
receptor antibody level was detected, which strongly sug-
gested the presence of myasthenia gravis. A fine needle
aspiration of the chest wall mass showed malignant cells.
The patient was referred to our hospital.
While awaiting surgical biopsy, she became acutely con-
fused. Laboratory values are shown in the Table. A diagno-
sis of SIADH was made and she improved with correction
of the hyponatremia. Later, however, she developed mus-
cle weakness and respiratory compromise despite treat-
ment with steroids and pyridostigmine. The patient
required mechanical ventilation and improved rapidly
with plasmapheresis. A biopsy of the mediastinal mass
revealed well-differentiated thymic carcinoma. The patient
was treated with etoposide and cisplatin and had an excel-
lent response. There was no recurrence of hyponatremia.
DISCUSSION
The systemic syndromes associated with thy-
momas include autoimmune or immune dis-
Thymoma Associated With Syndrome of
Inappropriate Antidiuretic Hormone
Secretion and Myasthenia Gravis
ALESSIA C. DONADIO, MD, KONSTANTIN H. DRAGNEV, MD, and GARY K. SCHWARTZ, MD, New York, NY
ABSTRACT: We describe the association of malignant thymoma with the syndrome of
inappropriate antidiuretic hormone secretion and myasthenia gravis. Hyponatremia has not
been reported associated with those tumors and our case should alert physicians about the
potential for a life-threatening complication.
From the Department of Medicine, Solid Tumor Section,
Memorial Sloan Kettering Cancer Center, New York, NY.
Reprint requests to Gary K. Schwartz, MD, Department of
Medicine, Solid Tumor Section, Memorial Sloan Kettering
Cancer Center, 1275 York Ave, New York, NY 10021.

Page 2

Donadio et al • THYMOMA, SIADH, AND MYASTHENIA GRAVIS
279
orders, endocrine disorders, non-thymic can-
cer, severe infections, and other diseases.
These conditions often lead to the discovery
of the tumor. Generally, 70% of thymoma
patients have immunologic disorders, 10%
have malignancy, 5% have an endocrine disor-
der, and the remaining have severe infections
or unrelated conditions. Between 30% to 50%
of thymoma patients have myasthenia gravis.
Some patients may exhibit more than one dis-
order,5as in our case.
In this patient, thymoma was associated with
myasthenia gravis, polymyositis, and SIADH.
While there are published reports of thymoma
and polymyositis, we could find no other
paper in the available literature describing the
phenomena of SIADH and thymoma. The
hyponatremia might have been due to the
presence of lung pathology, a typical stimulus
for the development of SIADH, or it could be
attributed to the patient’s thymoma. We favor
the latter, based on the effect of therapy. Our
patient had no further problems with hypona-
tremia once treatment was instituted and the
tumor rapidly responded. No other form of
long-term therapy was given and this suggests
a causal relationship rather than chance/tem-
poral association.
Classically, SIADH has been associated with
bronchogenic carcinoma with 2% incidence.
The mechanism involves ectopic production
of an ADH-like substance by the tumor.6-10The
pathophysiology of SIADH development in
thymoma remains to be elucidated. Never-
theless, it adds to the interesting associations
characteristic of this tumor. We hope to alert
physicians to look for early clues for a serious
complication in patients with thymoma.
References
1. Teitelbaum I, Kelleher S, Berl T: Diabetes insipidus and the
syndrome of inappropriate antidiuretic hormone secretion.
Diseases of the Kidney. Schrier RW, Gottschalk CW (eds).
Boston, Little Brown & Co, 5th Ed, 1993, pp 2503-2538
2. Robertson GL, Berl T: Pathophysiology of water metabo-
lism. The Kidney. Brenner BM, Rector FC Jr ( eds) .
Philadelphia, WB Saunders Co, 4th Ed, 1991, pp 677-736
3. Silverman P, Distelhorst CW: Metabolic emergencies in clini-
cal oncology. Se min Oncol 1989; 16:504-515
4. Glover DJ, Glick JH: Metabolic oncologic emergencies. CA
1987; 37:302-320
5. Rosenberg JC: Neoplasms of the mediastinum. Cancer
Principle s and Practice of Oncology. DeVita VT Jr, Hellman S,
Rosenberg SA (eds). Philadelphia, Lippincott, 3rd Ed,
1993, pp 759-775
6. Bunn PA, Minna JD: Paraneoplastic syndromes. Cancer
Principle s and Practice of Oncology. DeVita VT Jr, Hellman S,
Rosenberg SA (eds). Philadelphia, Lippincott, 3rd Ed,
1993, pp 2026-2063
7. Ebie N, Ryan W, Harris J: Metabolic emergencies in cancer
medicine. Me d Clin North Am1986; 70:1151-1166
8. Odell WD, Wolfsen AR: Humoral syndromes associated
with cancer. Ann Re v Me d1978; 29:379-406
9. Blackman MR, Rosen SW, Weitraub BD: Ectopic hormones.
Adv Inte rn Me d1978; 23:85-113
10. Rees LH: The biosynthesis of hormones by non-endocrine
tumors—a review. J Endocrinol 1975; 67:143-175
TABLE. Laboratory Values
Serum Values
Sodium 116 mEq/ L
Chloride 82 mEq/ L
Potassium 4.8 mEq/ L
Carbon dioxide 26 mEq/ L
Glucose 95 mg/ dL
Blood urea nitrogen 13 mg/ dL
Creatinine 0.5 mg/ dL
Osmolality 239 mOsmol/ kg
Calcium 9.3 mg/ dL
Uric acid 1.3 mg/ dL
Total protein 6.8 g/ dL
Albumin 4.2 g/ dL
Creatine phosphokinase 1,149 U/ L
Lactate dehydrogenase 480 U/ L
Cortisol 19.8 µg/ dL
Thyroid-stimulating hormone 3.99 µIU/ mL
Renin 1.6 ng/ mL/ hr
Creatinine clearance 99 mL/ min
Serum acetylcholine receptor antibody 28.9 nmol/ L
(normal less than 0.02 nmol/ L)
Antinuclear antibody–negative
Urine Values
Sodium 88 mEq/ L
Chloride 78 mEq/ L
Potassium 48 mEq/ L
Osmolality 434 mOsmol/ kg