Endocrine paraneoplastic syndromes PS

Syndrome of inappropriate ADH (SIADH)

The most common endocrine PS is due to inappropriate secretion of anti-diuretic hormone (arginine-vasopressin). Cancer types SCLS (10% of patients), pancreatic, prostate, NHL, HD. Presentation Often asymptomatic. CNS effects—fatigue, headaches; progressing to altered mental state, confusion, and seizures. Diagnosis Exclude non-malignant causes e.g. CNS disease (infection, trauma, vascular), pulmonary disease (infections, cystic lesions, asthma), drug-induced (thiazides, cytotoxics, narcotics); clinically euvolaemic; laboratory studies.

Treatment Fluid restriction (0.5-1.0 L/day); democlocycline (150- 300 mg 8 hourly).

Laboratory criteria for diagnosis of SIADH

♦ Normal serum albumin and glucose

♦ Serum hypo-osmolarity <275 mmol/Kg

♦ Urine osmolarity > serum osmolarity

♦ Non-suppressed ADH

Cushing's syndrome

Inappropriate overproduction of adenocorticotrophic hormone (ACTH) precursors.

Cancer types SCLC, NSCLC, pancreatic, thymic, and carcinoid tumours.

Presentation Rapid onset, marked weakness secondary to proximal myopathy, hyper-pigmentation, metabolic disturbances (e.g. hyper-glycaemia, hypokalaemic alkalosis).

Diagnosis Clinical features, especially hyper-pigmentation, myo-pathy; hypokalaemia and metabolic alkalosis; high 24-hr urinary cortisol, high plasma ACTH/precursors, no response to high-dose dexamethasone suppression or corticotropin-releasing hormone stimulation.

Treatment Specific anti-tumour treatment. Decrease cortisol secretion either surgically (bilateral adrenalectomy) or medically (metyrapone, octreotide, ketoconazole).

Hypercalcaemia

A common problem that in many cases is due to bony metastases.

True paraneoplastic hypercalcaemia is due to tumour production of parathyroid hormone-related protein. This syndrome is called

Humoral Hypercalcaemia of Malignancy (HHM).

Cancer types NSCLC, head and neck, renal, other squamous cancers.

(Rare in breast cancer where hypercalcaemia is usually due to bone metastases.)

Presentation Rapid onset of nausea, polyuria, polydipsia, dehydration, cardiac arrhythmias.

Diagnosis Serum Ca2+ >2.7 mmol/l, serum chloride low, hyper-calcuria, high urinary phosphate, low/undetectable plasma parathyroid hormone.

Treatment Saline hydration, IV pamidronate (60-120 mg).

Hypocalcaemia

Associated with tumours with lytic bone metastases (breast, prostate, and lung); can also occur with calcitonin-secreting medullary carcinomas of the thyroid. Usually asymptomatic. Rarely develop tetany and neuromuscular irritability. Treatment with calcium infusions.

Hypoglycaemia

Rarely caused by non-islet cell pancreatic tumours; often associated with mesenchymal tumours of the mediastinum and retroperitoneum and with hepatic cancers. Most likely cause is tumour production of the precursor to insulin-like growth factor II. Treatment with glucose infusions, tumour debulking.

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