A pheochromocytoma is a rare, catecholamine-secreting neuroendocrine tumor arising from the chromaffin cells of the adrenal medulla — the inner zone of the adrenal gland responsible for the “fight or flight” hormone response. The tumor produces and releases excess epinephrine (adrenaline) and/or norepinephrine (noradrenaline), causing the classic clinical triad of episodic severe headache, diaphoresis (sweating), and palpitations, typically accompanied by hypertensive crises that can be paroxysmal or sustained. The name itself describes the tumor’s behavior under the microscope: chromaffin cells stain a dusky (phaios) brown color (chroma) when exposed to chromium salts — a visible oxidation reaction unique to catecholamine-containing cells. The “10% tumor” rule — once taught as 10% bilateral, 10% extra-adrenal, 10% malignant, 10% familial — has been substantially revised: modern genomic data show 25-35% of pheochromocytomas have an identifiable germline mutation, associated with hereditary syndromes including von Hippel-Lindau (VHL) disease (Q85.8), multiple endocrine neoplasia type 2 (MEN2) (E31.21), neurofibromatosis type 1 (NF1) (Q85.01), and SDH (succinate dehydrogenase) gene mutations. When a phenochromocytoma arises outside the adrenal gland from extra-adrenal chromaffin tissue (sympathetic or parasympathetic ganglia), it is termed a paraganglioma — together, adrenal pheochromocytomas and extra-adrenal paragangliomas are grouped under the acronym PPGL (pheochromocytoma and paraganglioma). Surgical adrenalectomy — most commonly via laparoscopic approach (CPT 60650) — is the definitive curative treatment, but requires mandatory preoperative alpha-adrenergic blockade (phenoxybenzamine or doxazosin) for at least 10-14 days prior to surgery to prevent intraoperative hypertensive crisis from catecholamine surge during tumor manipulation. For AAPC-certified inpatient and profee coders, the single most important pheochromocytoma coding decision is benign vs. malignant: benign/uncertain tumors use the D35.0x neoplasm family; malignant pheochromocytoma maps to the C74.1x (adrenal medulla malignancy) family — and when the tumor is functionally active (catecholamine-secreting, as most are), E27.5 (adrenomedullary hyperfunction) must be sequenced in addition to the neoplasm code per the ICD-10-CM instructional note, not instead of it.
Describes the dark brownish-gray color that chromaffin cells acquire when oxidized by chromium salts in histological staining; alternate spelling pheo- (American) or phaeo- (British/Australian); same root in phaeomelanism (dark pigmentation)
Refers specifically to the chromaffin reaction — the color change produced when catecholamines in chromaffin granules are oxidized by chromium (Cr) salts; chromaffin = “affinity for chromium staining” (chrom- + Latin affinis); root also in chromatin, chromosome, chromatography
The combining form denoting cell; also root of cytology, cytoplasm, leukocyte, erythrocyte; in compound terms: cyto- refers to the cellular origin of the tumor (chromaffin cells)
Greek -ωμα (-ōma) — “a tumor, a swelling, a growth”; from the verb -oun — “to produce”
The ubiquitous tumor suffix in medical terminology; by convention, -oma implies a benign neoplasm (e.g., adenoma, lipoma, fibroma), though many important exceptions exist — melanoma, lymphoma, sarcoma, and pheochromocytoma itself can all be malignant despite the -oma suffix
The term pheochromocytoma was coined in 1912 by German pathologist Ludwig Pick to describe the characteristic brownish discoloration these tumors exhibited when treated with chromium-based fixatives — the chromaffin reaction. The adrenal medulla had been identified as the source of adrenaline (epinephrine) by John Jacob Abel and Jokichi Takamine around 1900-1901, and the connection between adrenomedullary tumors and hypertensive crises was established by Charles Mayo (of the Mayo Clinic family) in 1927, who performed the first successful surgical removal of a pheochromocytoma. The original “rule of 10s” (10% malignant, familial, bilateral, extra-adrenal) was a useful teaching heuristic but has been revised dramatically by 21st-century germline genomic studies — particularly following the identification of SDH gene mutations (SDHA, SDHB, SDHC, SDHD) as major drivers of hereditary PPGL, which pushed the hereditary fraction estimate from ~10% to ~25-35% of all cases. The abbreviation PPGL (pheochromocytoma and paraganglioma) was formally standardized in the 2014 Endocrine Society Clinical Practice Guidelines to reflect the shared chromaffin cell origin and overlapping management of both tumor types, unifying what had previously been described as two separate entities.
🔀 ALIASES / ALTERNATE TERMS
Term
Relationship
Pheo
Informal clinical abbreviation; acceptable in documentation shorthand; not a separately coded term
PPGL
Pheochromocytoma and paraganglioma — modern umbrella acronym; both adrenal (pheo) and extra-adrenal (paraganglioma) chromaffin tumors; standard in 2014+ literature and guidelines
Chromaffin cell tumor
Descriptive term emphasizing cell of origin; synonymous with pheochromocytoma; chromaffin = stains brown with chromium salts
Extra-adrenal chromaffin tumor — same cell of origin as pheo but arising outside the adrenal gland (organ of Zuckerkandl, carotid body, jugular, retroperitoneum); benign = D35.6; malignant = C75.5; coded separately from adrenal pheochromocytoma; included in PPGL grouping
ICD-10-CM term used in E27.5 — the functional code documenting catecholamine hypersecretion; code E27.5 WITH (not instead of) D35.0x or C74.1x per instructional note
Incidentaloma
An adrenal tumor found incidentally on imaging; coded E27.49 (other adrenocortical insufficiency) or D44.10-D44.12 (neoplasm of uncertain behavior) before workup; pheochromocytoma must be excluded biochemically before needle biopsy
Malignant pheochromocytoma
Defined by metastasis to non-chromaffin tissue (bone, liver, lung, lymph node); coded C74.11/C74.12 — malignancy cannot be determined by histology alone
VHL-associated pheochromocytoma
Hereditary pheo in von Hippel-Lindau syndrome; norepinephrine predominant; bilateral ~40-50%; coded D35.0x + Q85.8 (VHL)
Adrenal medulla — the inner zone of the adrenal gland; derived from neural crest cells; contains chromaffin cells; produces epinephrine (~80%) and norepinephrine (~20%); distinct from the adrenal cortex (cortisol, aldosterone, androgens); cortical tumors = adrenocortical adenoma/carcinoma, NOT pheochromocytoma
Chromaffin cells — the neuroendocrine cells of origin; named for their brown chromium staining; derived from sympathoadrenal neural crest progenitors; store catecholamines in chromaffin granules; found in adrenal medulla and extra-adrenal paraganglia
Catecholamines — epinephrine, norepinephrine, dopamine; the hormones produced and hypersecreated by pheochromocytoma; their metabolites (metanephrine, normetanephrine) are the biochemical markers of diagnosis; measured by CPT 82383 (urine catecholamines fractionated) and 82384 (plasma catecholamines fractionated)
Metanephrines — stable downstream metabolites of epinephrine (metanephrine) and norepinephrine (normetanephrine); preferred biochemical markers for PPGL diagnosis over catecholamines; plasma free fractionated metanephrines have ~96% sensitivity; 24-hour urine fractionated metanephrines have ~87% sensitivity; coded CPT 83835 (urine metanephrines)
Vanillylmandelic acid (VMA) — terminal catecholamine metabolite measurable in urine; historically the primary screening test; largely replaced by metanephrines due to lower sensitivity; 24-hour urine VMA CPT 84585
Alpha-adrenergic blockade — mandatory preoperative pharmacologic preparation; phenoxybenzamine (non-selective) or doxazosin (selective alpha-1); initiated 10-14 days pre-surgery to prevent intraoperative hypertensive crisis; without alpha blockade, surgical manipulation of the tumor can precipitate fatal catecholamine surge; beta blockade added ONLY after alpha blockade established
Adrenalectomy — the definitive surgical treatment; laparoscopic (CPT 60650) preferred for tumors <6 cm without evidence of local invasion; open (CPT 60540/60545) for large, malignant, or locally invasive tumors; partial adrenalectomy considered for bilateral disease (hereditary syndromes) to preserve adrenocortical function
MIBG (metaiodobenzylguanidine) scintigraphy — functional nuclear medicine imaging using radiolabeled MIBG (I-123 or I-131), which is taken up selectively by chromaffin tissue; used for staging, identifying extra-adrenal/metastatic disease, and MIBG-positive tumors eligible for targeted radionuclide therapy (I-131 MIBG); coded CPT 78800/78802 (radiopharmaceutical localization)
PET scan with DOTATATE (Ga-68) — somatostatin receptor PET; increasingly preferred over MIBG for PPGL staging and metastatic disease detection; superior sensitivity; coded CPT 78816 (whole body PET)
Von Hippel-Lindau (VHL) disease — hereditary tumor syndrome (VHL gene, chromosome 3p); associated with renal cell carcinoma, hemangioblastomas, retinal angiomas, and PPGL; pheo is norepinephrine-secreting; coded Q85.8
Multiple endocrine neoplasia type 2 (MEN2) — RET proto-oncogene mutation; MEN2A: medullary thyroid cancer + pheochromocytoma + primary hyperparathyroidism; MEN2B: adds mucosal neuromas and marfanoid habitus; coded E31.21 (MEN2A) / E31.22 (MEN2B)
Neurofibromatosis type 1 (NF1) — NF1 gene mutation; predominantly cutaneous neurofibromas and café-au-lait spots; pheo/paraganglioma in ~1-5% of NF1 patients; coded Q85.01
Succinate dehydrogenase (SDH) mutations — SDHB, SDHC, SDHD, SDHA; associated with extra-adrenal paraganglioma and metastatic PPGL; SDHB mutation in particular confers highest malignant potential (~30-40%); coded Z15.09 (susceptibility to other malignant neoplasm) when germline positive
Adrenal incidentaloma — adrenal mass >1 cm found incidentally on cross-sectional imaging; pheochromocytoma must be excluded biochemically (plasma free metanephrines) BEFORE needle biopsy in ALL adrenal incidentalomas — biopsy of an unprepared pheo can precipitate hypertensive crisis; adrenal incidentaloma coded E27.49 (pre-workup) or D44.10-D44.12 (neoplasm of uncertain behavior)
Hypertensive crisis — the life-threatening acute complication of pheochromocytoma from catecholamine surge; coded I16.1 (hypertensive emergency) — sequence I16.1 first, then pheo code; distinct from baseline hypertension secondary to pheo (I15.2)
CODING CORNER
📋 ICD-10-CM — Pheochromocytoma
⚠️ THE CRITICAL DUAL-CODE RULE: ICD-10-CM instructs you to code E27.5 (adrenomedullary hyperfunction/catecholamine hypersecretion) IN ADDITION TO the neoplasm code when the pheochromocytoma is functionally active — which the vast majority are. The E27.5 instructional note says “Code also, if applicable: malignant pheochromocytoma (C74.1-) [or] pheochromocytoma (benign) (D35.0-).” This means the neoplasm code (D35.0x or C74.1x) should be sequenced FIRST as the principal/first-listed diagnosis, with E27.5 as an additional code documenting functional activity. Do NOT use E27.5 alone for pheochromocytoma without the neoplasm code. Parent codes D35.0 (benign) and C74.1 (malignant medulla) are NOT billable — the full laterality code is required.
Benign neoplasm of right adrenal gland (includes benign pheochromocytoma, right adrenal; most common single-code for sporadic unilateral right-sided pheo — add E27.5 when functionally active)
Malignant neoplasm of medulla of right adrenal gland (malignant pheo — defined by metastasis to non-chromaffin tissue; cannot be determined by histology alone; add E27.5 when catecholamine-secreting)
Adrenomedullary hyperfunction (catecholamine hypersecretion; adrenomedullary hyperplasia — code ADDITIONALLY with D35.0x or C74.1x; includes catecholamine hypersecretion by instructional note; do NOT use alone without neoplasm code)
Benign neoplasm of aortic body and other paraganglia (benign extra-adrenal paraganglioma — organ of Zuckerkandl, sympathetic chain, retroperitoneum; no laterality required)
Neoplasm of uncertain behavior of unspecified adrenal gland (adrenal incidentaloma — uncertain behavior pre-workup; or when pathology is indeterminate; avoid if benign/malignant confirmed)
Hypertension secondary to endocrine disorders (sustained hypertension caused by pheochromocytoma catecholamine excess — sequence D35.0x or C74.1x first; I15.2 additional; do NOT use primary HTN codes I10 when pheo is documented etiology)
Hypertensive emergency (acute catecholamine surge/hypertensive crisis — sequence I16.1 FIRST as the reason for encounter when crisis is the presenting condition; add D35.0x/C74.1x and E27.5)
Hereditary Syndromes — Code Additionally When Documented
Personal history of malignant neoplasm of other sites (history of malignant pheochromocytoma — use for surveillance visits after curative-intent surgery when no current evidence of disease)
Encounter for follow-up examination after completed treatment for malignant neoplasm (principal code for surveillance visit post-adrenalectomy for malignant pheo)
🔧 CPT Codes — Pheochromocytoma Procedures
⚠️ CPT 60540 and 60545 are designated “separate procedure” codes — they can be restricted from billing alongside other CPT codes performed at the same session. CPT 60650 (laparoscopic adrenalectomy) is the standard of care for most pheochromocytomas and does NOT carry the same “separate procedure” restriction as 60540/60545. Do NOT bill CPT 60540 or 60545 together with other abdominal/retroperitoneal procedures on the same claim without strong medical documentation and modifier support — they will bundle. Needle biopsy (CPT 60699 or image-guided 49180) of an adrenal mass is CONTRAINDICATED before pheochromocytoma is biochemically excluded — document pre-biopsy metanephrine results in the record.
Laparoscopy, surgical, with adrenalectomy, partial or complete, or exploration of adrenal gland with or without biopsy, transabdominal, lumbar or dorsal (gold-standard approach for pheo ≤6 cm; includes partial adrenalectomy for bilateral hereditary disease; most commonly reported pheo surgery code)
Adrenalectomy, partial or complete, or exploration of adrenal gland with or without biopsy, transabdominal, lumbar or dorsal (OPEN adrenalectomy — “separate procedure” designation; large tumors, malignant/invasive, or conversion from laparoscopic; verify NCCI before billing with other abdominal CPTs)
Adrenalectomy, partial or complete, or exploration of adrenal gland with or without biopsy, transabdominal, lumbar or dorsal; with excision of adjacent retroperitoneal tumor (open adrenalectomy + resection of adjacent retroperitoneal disease — malignant pheo with local extension; “separate procedure” designation — same NCCI cautions)
Level V — Surgical pathology, gross and microscopic examination (adrenal gland resection specimen — required for all adrenalectomy specimens; Level V for resection of neoplasm; includes chromaffin immunostains confirming pheochromocytoma diagnosis; separately billable from surgical CPT)
Immunohistochemistry or immunocytochemistry, per specimen; initial single antibody stain procedure (chromaffin cell immunostains: chromogranin A, synaptophysin, PHOX2B; supports pheochromocytoma diagnosis confirmation on surgical specimen)
Immunohistochemistry or immunocytochemistry, per specimen; each additional single antibody stain procedure (additional immunostains beyond first; bill with 88342 as primary + 88341 for each additional antibody)
Catecholamines; fractionated (dopamine, epinephrine, norepinephrine), urine (24-hour urine catecholamines — historically standard; less sensitive than metanephrines; still ordered but not preferred first-line per current guidelines)
Catecholamines; fractionated (dopamine, epinephrine, norepinephrine), blood (plasma catecholamines fractionated — less sensitive than plasma free metanephrines; not recommended as first-line per CAP/ARUP guidelines)
CT abdomen and pelvis with contrast (primary anatomic imaging for adrenal mass characterization; <10 HU on non-contrast = lipid-rich adenoma; pheo typically >10 HU; adrenal protocol CT standard for incidentaloma workup)
Radiopharmaceutical localization of tumor, inflammatory process or distribution of radiopharmaceutical agent(s); limited area (I-123 or I-131 MIBG scintigraphy — chromaffin-specific functional imaging for PPGL localization, metastatic staging, and MIBG-avidity assessment for radionuclide therapy eligibility)
Positron emission tomography (PET); whole body (Ga-68 DOTATATE PET — somatostatin receptor PET; superior sensitivity to MIBG for PPGL; increasingly first-line for metastatic disease staging)
Right side — required for all unilateral adrenalectomy CPT codes; 60650, 60540, 60545 all require laterality; right adrenal = right-sided adrenalectomy
Increased procedural complexity — large tumor (>6 cm), malignant local invasion, conversion from laparoscopic to open, IVC involvement, or morbid obesity significantly increasing operative difficulty; requires special report; increases reimbursement above base RVU
Multiple procedures — secondary procedures at same session; e.g., retroperitoneal lymphadenectomy (38780) for malignant pheo staging performed with adrenalectomy (60650); reduces payment on secondary code
Distinct procedural service — e.g., 88342 (IHC first antibody) and 88341 (IHC additional) are distinct staining procedures on adrenalectomy specimen; or MIBG imaging (78802) as distinct from CT abdomen (74177) on same date
Reduced services — laparoscopic adrenalectomy converted to open mid-procedure due to bleeding; when open component was significantly abbreviated; use with documentation of reason for conversion
Unplanned return to OR within global period — post-adrenalectomy hemorrhage, adrenal bed hematoma evacuation, or wound complication within 90-day global period of original adrenalectomy
Staged procedure — planned contralateral adrenalectomy in bilateral hereditary pheo when staged surgically (e.g., right adrenalectomy first; left adrenalectomy planned 3-6 months later within global period)
⚠️ Coding Notes & Payer Guidance
The dual-code requirement — D35.0x/C74.1x AND E27.5: The ICD-10-CM instructional note under E27.5 explicitly states “Code also, if applicable: malignant pheochromocytoma (C74.1-)” and “pheochromocytoma (benign) (D35.0-).” This is a Code Also instruction (not Excludes1 or Excludes2), meaning BOTH codes are required simultaneously when functional activity (catecholamine hypersecretion) is present. Sequence the neoplasm code (D35.01, C74.11, etc.) as the principal/first-listed diagnosis and E27.5 as an additional code. OmittingE27.5 when the patient has documented catecholamine hypersecretion or hypertension secondary to pheo is an undercoding error that reduces DRG weight on inpatient cases.
Benign vs. malignant — it cannot be determined by pathology alone: Malignant pheochromocytoma (C74.11/C74.12) is defined in the WHO Classification of Tumors (2022) exclusively by the presence of metastasis to non-chromaffin tissue (lymph nodes, bone, liver, lung). Histopathology CANNOT reliably distinguish benign from malignant chromaffin tumors — there is no histologic criterion that predicts malignancy with certainty. Therefore, if the pathology report says “pheochromocytoma” without documented metastasis, the correct code is D35.01/D35.02 (benign), not C74.1x. Only when metastatic disease is documented (radiologically or pathologically confirmed) should C74.1x be applied. SDHB mutation is a risk factor for malignancy but does not by itself justify the malignant code without confirmed metastasis.
CPT 60540 / 60545 “separate procedure” designation — bundle risk: Both open adrenalectomy codes carry the CPT “separate procedure” designation, meaning payers may refuse to reimburse them when reported with other intra-abdominal surgical procedures performed at the same session. This restriction does NOT apply to 60650 (laparoscopic adrenalectomy). When open adrenalectomy for malignant pheo requires concurrent retroperitoneal lymphadenectomy or adjacent organ resection, thorough operative report documentation of the distinct and separately necessary nature of each component is essential to support additional CPT claims alongside 60540/60545.
I15.2 vs. I10 — secondary hypertension is not primary hypertension: When a pheochromocytoma is the documented cause of the patient’s hypertension, I15.2 (hypertension secondary to endocrine disorders) must be used — NOT I10 (essential/primary hypertension). Using I10 for pheo-related hypertension is technically incorrect and will understate the complexity of the clinical picture on inpatient DRG assignment. After successful adrenalectomy and tumor cure, if hypertension resolves, discontinue I15.2 and I10 from future encounters. If hypertension persists post-cure (~30% of patients develop permanent primary HTN), reclassify to I10.
Adrenal incidentaloma — never biopsy before biochemical pheo exclusion: Any adrenal mass found incidentally should have pheochromocytoma excluded with plasma free fractionated metanephrines (CPT 83835) before proceeding to image-guided needle biopsy. Needle biopsy of an unprepared pheochromocytoma can precipitate a fatal hypertensive crisis from catecholamine release. This is a clinical safety standard, not just a coding note — but documenters should ensure the pre-biopsy metanephrine results are in the record to demonstrate appropriate workup sequence if audited.
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