# Secondary Polycythaemia and Erythrocytosis

> Secondary polycythaemia for NEET-PG Medicine covering erythropoietin levels, hypoxic and tumour causes, JAK2 testing and differences from polycythaemia vera.

- Canonical URL: https://prepelephant.com/topics/neet-pg/medicine/secondary-polycythaemia-and-erythrocytosis
- Exam / course: NEET-PG · Subject: Medicine
- Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team
- First published: 2026-10-14
- Last updated: 2026-10-14
- Reference basis: Harrison's Principles of Internal Medicine; Hoffbrand's Essential Haematology
- How to cite: "Secondary Polycythaemia and Erythrocytosis", PrepElephant, https://prepelephant.com/topics/neet-pg/medicine/secondary-polycythaemia-and-erythrocytosis

## Direct answer

Secondary polycythaemia is an increase in red cell mass driven by excess erythropoietin rather than by a primary marrow disorder. Common causes include chronic hypoxia from lung disease, high altitude or cyanotic heart disease, erythropoietin-secreting tumours and exogenous androgens. Serum erythropoietin is the key test: it is raised or inappropriately normal in secondary causes but low in polycythaemia vera.

## What you must remember

- **Definition:** a true rise in red cell mass, distinct from relative erythrocytosis caused by plasma loss, which concentrates the blood without increasing the cell mass.
- **Serum erythropoietin:** raised or inappropriately normal in secondary causes but low in polycythaemia vera, making it the key discriminator.
- **JAK2 V617F:** a gain-of-function mutation found in most patients with polycythaemia vera; its absence does not fully exclude a myeloproliferative cause.
- **Hypoxic causes:** COPD, high altitude, obstructive sleep apnoea, cyanotic congenital heart disease and hypoventilation syndromes raise erythropoietin.
- **Erythropoietin-secreting tumours:** renal cell carcinoma, hepatocellular carcinoma, cerebellar haemangioblastoma and uterine leiomyoma are classic examples.
- **Exogenous androgens:** testosterone and anabolic steroids stimulate erythropoiesis, so a drug history is essential.
- **Gaisbock syndrome:** classically described relative erythrocytosis in obese, hypertensive smokers with a normal red cell mass, reflecting reduced plasma volume.
- **Renal artery stenosis:** renal hypoperfusion can raise erythropoietin, a cause to consider in hypertensive patients.

## A diagnostic pathway from raised haemoglobin

Raised haemoglobin is a finding rather than a diagnosis, and it is confirmed before any treatment is started. The pathway first separates true erythrocytosis from dehydration, then uses erythropoietin to split secondary from primary causes.

1. **Confirm a true rise:** Repeat the full blood count after rehydration, since dehydration or plasma loss can inflate haemoglobin without increasing the red cell mass.
2. **Measure serum erythropoietin:** A raised or inappropriately normal level points to a secondary cause, whereas a low level with raised haemoglobin favours polycythaemia vera.
3. **Look for hypoxia:** Check arterial blood gases, oxygen saturation, carboxyhaemoglobin and a sleep study where suspected, because hypoxia is the commonest driver of secondary erythrocytosis.
4. **Search for tumours and drugs:** Imaging of the kidneys, liver and cerebellum, along with a careful androgen history, identifies erythropoietin-secreting tumours and iatrogenic causes.
5. **Send JAK2 testing:** When erythropoietin is low, JAK2 V617F testing and bone marrow examination pursue polycythaemia vera, which needs its own management.
6. **Treat the driver:** Correct hypoxia, stop androgens and treat the tumour; venesection is not a routine treatment for secondary causes.

## Where the exam tries to catch you

Most traps here involve treating the number rather than its cause.

- **Trap:** Starting venesection for every raised haemoglobin — **Correct:** phlebotomy treats the red cell mass in polycythaemia vera, while secondary causes need correction of the driver such as hypoxia or androgens.
- **Trap:** Diagnosing polycythaemia vera from haemoglobin alone — **Correct:** serum erythropoietin and JAK2 V617F testing separate primary from secondary disease before a myeloproliferative diagnosis is made.
- **Trap:** Missing androgens or erythropoietin in an athlete — **Correct:** a detailed drug history for testosterone, anabolic steroids and erythropoietin is essential, since doping can produce secondary erythrocytosis.
- **Trap:** Assuming high haemoglobin in a smoker is always a true rise in red cell mass — **Correct:** smoking causes a genuine secondary erythrocytosis through carboxyhaemoglobin, but a relative rise as in Gaisbock syndrome also occurs, so measured red cell mass may be needed.

## Frequently asked questions

### How does serum erythropoietin help distinguish secondary polycythaemia from polycythaemia vera?
Serum erythropoietin is raised or inappropriately normal in secondary polycythaemia, because the kidney responds to hypoxia or tumour secretion. In polycythaemia vera, erythropoietin is suppressed because the marrow proliferates independently. A low level with raised haemoglobin therefore favours primary disease.

### Which tumours cause secondary polycythaemia through erythropoietin production?
Renal cell carcinoma, hepatocellular carcinoma, cerebellar haemangioblastoma and uterine leiomyoma can secrete erythropoietin and cause secondary polycythaemia. Renal cell carcinoma is the classic example in clinical teaching. Imaging of the abdomen and cerebellum is directed by the clinical picture.

### Which genetic mutation is characteristic of polycythaemia vera?
The JAK2 V617F mutation is characteristic of polycythaemia vera and is found in most patients. It causes constitutive JAK-STAT signalling that drives erythroid proliferation independent of erythropoietin. Its presence distinguishes primary from secondary erythrocytosis in the diagnostic work-up.

### Why does living at high altitude cause secondary polycythaemia?
Low ambient oxygen at high altitude reduces arterial oxygen saturation, which stimulates the kidney to produce more erythropoietin. Over weeks, this raises the red cell mass to compensate. Chronic mountain sickness is an exaggerated form of this response.

### What is Gaisbock syndrome?
Gaisbock syndrome is a relative erythrocytosis seen in obese, hypertensive smokers, with raised haemoglobin but a normal red cell mass. It results from reduced plasma volume rather than an increased number of red cells. Management focuses on smoking cessation, blood pressure and weight control.