What can cause polydipsia, polyuria, vertigo, headaches, and fluctuating blood pressure?

Differential Diagnosis of Polydipsia, Polyuria, Vertigo, Headaches, and Fluctuating Blood Pressure

This constellation of symptoms should immediately raise concern for endocrine disorders, particularly diabetes mellitus, diabetes insipidus, hypercalcemia of malignancy, or pheochromocytoma, with central nervous system pathology as a critical alternative diagnosis.

Primary Endocrine Causes

Diabetes Mellitus (Type 1 or Type 2)

• Polyuria and polydipsia are hallmark symptoms of diabetes mellitus, with approximately one-third of children with type 1 diabetes presenting with these classic symptoms 1
• Headaches and fluctuating blood pressure can occur secondary to hyperglycemia and associated metabolic derangements 1
• Vertigo may result from diabetic autonomic neuropathy affecting blood pressure regulation or from hypoglycemic episodes 1
• Diagnostic approach: Measure fasting plasma glucose, 2-hour oral glucose tolerance test, or HbA1c; values ≥126 mg/dL fasting, ≥200 mg/dL at 2 hours, or HbA1c ≥6.5% confirm diabetes 1

Diabetes Insipidus (Central or Nephrogenic)

• Central diabetes insipidus presents with severe polyuria (often >3 L/day in adults) and compensatory polydipsia, with serum osmolality typically >300 mOsm/kg H₂O while urine remains inappropriately diluted at <200 mOsm/kg H₂O 2
• Headaches are a prominent feature when caused by intracranial lesions such as germinoma, craniopharyngioma, or Langerhans cell histiocytosis 3
• Vertigo and fluctuating blood pressure can occur from dehydration-induced hypovolemia or from the underlying intracranial pathology 2
• Diagnostic approach: Hypertonic saline test with plasma copeptin measurement has emerged as the gold standard, replacing the water deprivation test 4
• MRI may reveal loss of posterior pituitary hyperintensity and identify structural lesions 3

Hypercalcemia of Malignancy

• Polyuria and polydipsia are cardinal features, occurring in 10-25% of patients with lung cancer, most commonly squamous cell type 1
• Headaches result from the hypercalcemia itself, particularly when severe (>14 mg/dL) 1
• Fluctuating blood pressure manifests as hypotension in severe cases, with bradycardia when calcium exceeds 14 mg/dL 1
• Vertigo occurs secondary to dehydration, confusion, and metabolic derangement 1
• Diagnostic approach: Measure serum calcium (corrected for albumin), intact PTH (suppressed in malignancy), PTHrP (elevated), and 1,25-dihydroxyvitamin D levels 1

Checkpoint Inhibitor-Associated Diabetes Mellitus (CIADM)

• Acute onset of polyuria, polydipsia, weight loss, and lethargy characterize this autoimmune beta-cell destruction in patients receiving immunotherapy 1
• Headaches and fluctuating blood pressure can accompany diabetic ketoacidosis or severe hyperglycemia 1
• Diagnostic approach: Check urine ketones, acid-base status, glucose, and send GAD65 antibodies, insulin, and C-peptide levels (though treatment should not be delayed) 1
• This requires immediate insulin therapy and endocrinology consultation 1

Central Nervous System Causes

Posterior Circulation Stroke or Vertebrobasilar Insufficiency

• Vertigo with severe postural instability and headache is a red flag for vertebrobasilar stroke, which can present with isolated vertigo preceding stroke by weeks to months 5
• Episodes typically last <30 minutes without hearing loss 5
• Fluctuating blood pressure occurs from brainstem involvement affecting autonomic centers 5
• Polyuria and polydipsia are less prominent but can occur with hypothalamic involvement 5
• Critical distinction: Nystagmus that does not fatigue, is not suppressed by gaze fixation, and is purely vertical without torsional component indicates central pathology 5
• Approximately 25% of patients with acute vestibular syndrome have cerebrovascular disease, rising to 75% in high vascular risk cohorts 5

Pituitary Lesions (Hypophysitis, Adenoma, Craniopharyngioma)

• Headache and visual field changes are characteristic of pituitary disease 1
• Central diabetes insipidus causes polyuria and polydipsia 3
• Vertigo can result from associated hydrocephalus or mass effect 3
• Fluctuating blood pressure may occur from ACTH deficiency (secondary adrenal insufficiency) 1

Secondary Metabolic Causes

Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

• SIADH causes hyponatremia with symptoms including headache, confusion, and potentially seizures 1
• Paradoxically, patients have concentrated urine (>300 mOsm/kg) with urinary sodium >40 mEq/L and serum osmolality <275 mOsm/kg 1
• Vertigo results from cerebral edema and hyponatremia 1
• Polydipsia may be present, but polyuria is notably absent (this is a key distinguishing feature) 1
• Most commonly associated with small cell lung cancer 1

Hyperthyroidism/Thyrotoxicosis

• Weight loss, palpitations, heat intolerance, tremors, anxiety, and diarrhea characterize the hypermetabolic state 1
• Increased fluid turnover can cause relative polyuria and compensatory polydipsia 1
• Headaches and fluctuating blood pressure (typically hypertension with wide pulse pressure) are common 1
• Vertigo can occur from the hypermetabolic state 1
• Diagnostic approach: Measure TSH (low/normal) and free T4 or T3 (elevated); consider thyroid antibodies (TRAb, TSI, TPO) 1

Critical Diagnostic Algorithm

Step 1: Immediate Risk Stratification

• Measure serum sodium, glucose, calcium, and creatinine immediately 1, 2
• Check vital signs including orthostatic blood pressure 5
• Assess for neurological red flags: severe postural instability, new focal deficits, altered mental status 5

Step 2: Urine Analysis

• Urine specific gravity and osmolality are critical:
  • Low (<1.005 or <200 mOsm/kg) suggests diabetes insipidus or psychogenic polydipsia 2, 4
  • Inappropriately concentrated (>300 mOsm/kg) with low serum sodium suggests SIADH 1
  • Glucosuria indicates diabetes mellitus 1

Step 3: Neurological Examination

• Perform Dix-Hallpike maneuver to differentiate peripheral from central vertigo 5
• Peripheral (BPPV): torsional nystagmus with latency, fatigability, resolves within 60 seconds 5
• Central: purely vertical nystagmus without torsional component, immediate onset, persistent, not suppressed by visual fixation 5
• Any of the following mandate urgent neuroimaging: severe postural instability with falling, new-onset severe headache with vertigo, downbeating nystagmus without torsional component, any additional neurological symptoms 5

Step 4: Endocrine Workup

• If glucose elevated: HbA1c, consider C-peptide and autoantibodies if type 1 suspected 1
• If calcium elevated: intact PTH, PTHrP, vitamin D metabolites 1
• If polyuria with dilute urine: hypertonic saline test with copeptin measurement 4
• Thyroid function tests (TSH, free T4) 1
• Morning cortisol and ACTH if adrenal insufficiency suspected 1

Step 5: Imaging

• Brain MRI with contrast if any central vertigo features or unexplained diabetes insipidus 5, 3
• Chest imaging if hypercalcemia or SIADH suspected (evaluate for malignancy) 1
• Pituitary protocol MRI if central diabetes insipidus or pituitary dysfunction 3

Common Pitfalls to Avoid

• Do not dismiss isolated vertigo as benign peripheral vertigo without careful neurological examination, as 10% of cerebellar strokes present similarly to peripheral vestibular disorders 5
• Do not restrict water access in polyuric patients, as this can lead to life-threatening hypernatremic dehydration 2, 6
• Do not use HbA1c alone in conditions with increased red blood cell turnover (sickle cell disease, recent blood loss); use plasma glucose criteria only 1
• Do not overlook medication-induced causes: loop diuretics, glucocorticoids, lithium, demeclocycline, and many antihypertensives can cause polyuria or vertigo 1, 6
• Do not assume diabetes mellitus is type 2 in adults; checkpoint inhibitor-associated diabetes and type 1 diabetes occur at all ages and require different management 1