Paraneoplastic manifestation of severe hyponatremia caused by Syndrome of inappropriate antidiuretic hormone secretion (SIADH) in small cell lung carcinoma
Date Issued
2018-01
Author(s)
Abstract
Introduction
Paraneoplastic syndromes are a group of clinical disorders, associated with malignant diseases, not
directly related to the localization of primary or metastatic tumors. These syndromes are described
in lymphoma, thymoma, mesothelioma, Ewing’s sarcoma, and a variety of carcinomas.
Approximately 70% of malignancy-related cases are as result of small cell lung cancer (SCLC).
Associated with lung cancer, include: neurologic, endocrine, dermatologic, rheumatologic,
hematologic, ophthalmological syndromes, glomerulopathy and coagulopathy (Trousseau’s
syndrome). Small-cell lung carcinoma is an aggressive form of lung cancer, strongly associated with
cigarette smoking, usually presents in central airways, infiltrating the submucosa. Common
symptoms: cough, dyspnea, weight loss, fatigue. Over 70% of patients present with metastatic
disease: liver, adrenals, bone, brain. Due to its neuroendocrine nature, small-cell carcinomas can
produce ectopic hormones, adrenocorticotropic hormone and anti-diuretic hormone (ADH, also
called vasopressin). Lambert-Eaton myasthenic syndrome is paraneoplastic condition linked to
small-cell carcinoma. Published data suggest that the average incidence of clinically manifested
SIADH in patients with newly diagnosed small cell lung cancer is only 4%. Syndrome of inappropriate
anti-diuretic hormone secretion (SIADH) was first associated with malignancy when described in two
patients with bronchogenic carcinoma in 1957.
Case Presentation
A 60 year old male, smoker for 30 years (48 pack-per-year smoking history), was
hospitalized because of one month history of weakness, dry cough, chest pain, syncope. Physical
examination - normotensive, afebrile, heart rate 100/min, weight 79 kg. Rhythmic heart action. Lung
auscultation revealed diminished breath sound in right lung. Abdomen: bowel sounds present, with
no organomegaly. Extremities: no edema, warm, pulses positive. Initial 12 lead ECG was normal.
Laboratory results - hyponatremia 117mmol/L, with normal potassium, calcium, magnesium,
phosphorus, urea, creatinin, uric acid, proteins in serum and urine, tumour markers (normal CEA,
CA-19-9, AFP, PSA, Cyfra 21-1), mildly elevated NSE, reduced plasma osmolality 248,3mosm/kg
and urine sodium below 40mEq/L/24 hours.
Chest X-ray presented parenchymal consolidation in right lung in communication with enlarged right
hilus (Figure 1).
The patient undrewent bronchoscopy and biopsy. Bronchoscopy revealed paresis of right vocal cord,
shortened main carina, left bronchial tree was normal. Right bronchial tree with edematous carina
superior lat.dex., submucous infiltration with stenosis of anterior branch of upper lobe and
intermediate bronchus (Figure 3, 4).
Patohystology morphologic features were consistent with small cell lung carcinoma (Figure 5).
Lung CT scan presented hypodense parenchimal change next to right hilus with compression of
right bronchus and atelectasis, with mediastinal lymhadenopathy (Figure 2).Also for staging abdominal ultrasound was performed, organs were normal, only enlarged adrenal
glands were detected.
After hyponatremia was corrected, restricted fluid intake (maximum 1000ml/day), and health status
improven, further treatment was continued at Institute of Oncology.
Discussion
Ectopic production of large amounts of ADH leads to syndrome of inappropriate antidiuretic
hormone hypersecretion (SIADH), defined by hyponatremia, water retention, hypo-osmolality. ADH
plays an important role in regulating the balance of fluids. It lowers the amount of urine the and
increases the amount of water the kidneys take up. SIADH is characterized by neurological
and psychiatric symptoms attributable to cerebral edema. Symptoms may be mild and vague at first,
but tend to build. Severe cases may involve these symptoms: irritability and restlessness, loss of
appetite, cramps, nausea and vomiting, muscle weakness, confusion, hallucination, personality
changes, seizures, stupor, coma. The goal of treatment is very gradual coorrection of hyponatremia
and fluid restriction. Hyponatremia inoncology practice, may be a negative prognostic factor in
cancer patients based on a systematic analysis of published studies.
Paraneoplastic syndromes are a group of clinical disorders, associated with malignant diseases, not
directly related to the localization of primary or metastatic tumors. These syndromes are described
in lymphoma, thymoma, mesothelioma, Ewing’s sarcoma, and a variety of carcinomas.
Approximately 70% of malignancy-related cases are as result of small cell lung cancer (SCLC).
Associated with lung cancer, include: neurologic, endocrine, dermatologic, rheumatologic,
hematologic, ophthalmological syndromes, glomerulopathy and coagulopathy (Trousseau’s
syndrome). Small-cell lung carcinoma is an aggressive form of lung cancer, strongly associated with
cigarette smoking, usually presents in central airways, infiltrating the submucosa. Common
symptoms: cough, dyspnea, weight loss, fatigue. Over 70% of patients present with metastatic
disease: liver, adrenals, bone, brain. Due to its neuroendocrine nature, small-cell carcinomas can
produce ectopic hormones, adrenocorticotropic hormone and anti-diuretic hormone (ADH, also
called vasopressin). Lambert-Eaton myasthenic syndrome is paraneoplastic condition linked to
small-cell carcinoma. Published data suggest that the average incidence of clinically manifested
SIADH in patients with newly diagnosed small cell lung cancer is only 4%. Syndrome of inappropriate
anti-diuretic hormone secretion (SIADH) was first associated with malignancy when described in two
patients with bronchogenic carcinoma in 1957.
Case Presentation
A 60 year old male, smoker for 30 years (48 pack-per-year smoking history), was
hospitalized because of one month history of weakness, dry cough, chest pain, syncope. Physical
examination - normotensive, afebrile, heart rate 100/min, weight 79 kg. Rhythmic heart action. Lung
auscultation revealed diminished breath sound in right lung. Abdomen: bowel sounds present, with
no organomegaly. Extremities: no edema, warm, pulses positive. Initial 12 lead ECG was normal.
Laboratory results - hyponatremia 117mmol/L, with normal potassium, calcium, magnesium,
phosphorus, urea, creatinin, uric acid, proteins in serum and urine, tumour markers (normal CEA,
CA-19-9, AFP, PSA, Cyfra 21-1), mildly elevated NSE, reduced plasma osmolality 248,3mosm/kg
and urine sodium below 40mEq/L/24 hours.
Chest X-ray presented parenchymal consolidation in right lung in communication with enlarged right
hilus (Figure 1).
The patient undrewent bronchoscopy and biopsy. Bronchoscopy revealed paresis of right vocal cord,
shortened main carina, left bronchial tree was normal. Right bronchial tree with edematous carina
superior lat.dex., submucous infiltration with stenosis of anterior branch of upper lobe and
intermediate bronchus (Figure 3, 4).
Patohystology morphologic features were consistent with small cell lung carcinoma (Figure 5).
Lung CT scan presented hypodense parenchimal change next to right hilus with compression of
right bronchus and atelectasis, with mediastinal lymhadenopathy (Figure 2).Also for staging abdominal ultrasound was performed, organs were normal, only enlarged adrenal
glands were detected.
After hyponatremia was corrected, restricted fluid intake (maximum 1000ml/day), and health status
improven, further treatment was continued at Institute of Oncology.
Discussion
Ectopic production of large amounts of ADH leads to syndrome of inappropriate antidiuretic
hormone hypersecretion (SIADH), defined by hyponatremia, water retention, hypo-osmolality. ADH
plays an important role in regulating the balance of fluids. It lowers the amount of urine the and
increases the amount of water the kidneys take up. SIADH is characterized by neurological
and psychiatric symptoms attributable to cerebral edema. Symptoms may be mild and vague at first,
but tend to build. Severe cases may involve these symptoms: irritability and restlessness, loss of
appetite, cramps, nausea and vomiting, muscle weakness, confusion, hallucination, personality
changes, seizures, stupor, coma. The goal of treatment is very gradual coorrection of hyponatremia
and fluid restriction. Hyponatremia inoncology practice, may be a negative prognostic factor in
cancer patients based on a systematic analysis of published studies.
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