Ectopic Fat Pads: The Buffalo Hump and Dorsocervical Fat Pad as Diagnostic Signposts

 

Ectopic Fat Pads: The Buffalo Hump and Dorsocervical Fat Pad as Diagnostic Signposts in Internal Medicine

Dr Neeraj Manikath , claude.ai

Abstract

The dorsocervical fat pad, colloquially termed "buffalo hump," represents a distinctive pattern of ectopic fat accumulation that serves as a critical physical examination finding in internal medicine. While often associated with Cushing's syndrome, this sign has a limited but important differential diagnosis that every internist must master. This review explores the pathophysiology, clinical differentiation, and diagnostic approach to patients presenting with dorsocervical fat accumulation, with particular emphasis on distinguishing hypercortisolism from its modern mimics.

Introduction

Physical examination remains an irreplaceable diagnostic tool in the era of advanced imaging and laboratory medicine. Few physical signs offer as direct a window into underlying pathophysiology as the dorsocervical fat pad. This abnormal fat accumulation at the posterior neck and supraclavicular regions represents more than a cosmetic concern—it is a metabolic billboard announcing profound endocrine or iatrogenic disturbance.

The significance of recognizing this sign cannot be overstated. Cushing's syndrome, though rare with an incidence of 0.7-2.4 per million population annually, carries substantial morbidity and mortality when undiagnosed. The presence of a buffalo hump in combination with other stigmata of hypercortisolism should trigger immediate diagnostic evaluation. However, the modern clinician must also recognize important mimics, particularly HIV-associated lipodystrophy, which has transformed the differential diagnosis since the advent of antiretroviral therapy.

Pathophysiology: The Glucocorticoid Receptor and Regional Fat Distribution

The Molecular Basis of Ectopic Fat Deposition

Understanding why excess cortisol produces characteristic fat redistribution requires appreciation of glucocorticoid receptor (GR) biology and adipocyte heterogeneity. Glucocorticoid receptors are ubiquitously expressed, but their density and the local enzymatic milieu vary substantially across different adipose depots.

The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts inactive cortisone to active cortisol within adipose tissue. This enzyme is preferentially expressed in visceral, dorsocervical, and facial adipose depots. In states of glucocorticoid excess—whether endogenous or exogenous—these regions become sites of preferential lipogenesis and adipocyte hypertrophy. The mechanism involves multiple pathways: glucocorticoids enhance lipoprotein lipase activity, increase expression of adipogenic transcription factors (including C/EBPα and PPARγ), and synergize with insulin to promote triglyceride accumulation.

Simultaneously, cortisol promotes lipolysis in peripheral subcutaneous fat depots, particularly in the extremities. This explains the characteristic body habitus of Cushing's syndrome: central obesity with proximal muscle wasting and thin extremities. The supraclavicular regions, rich in brown adipose tissue in infancy, become sites of white adipose accumulation under the influence of chronic hypercortisolism.

Clinical Pearl: The "lemon on sticks" appearance—truncal obesity with thin limbs—is pathognomonic when severe, but early cases may show subtle redistribution that becomes apparent only with serial photographs.

Why the Dorsocervical Region?

The predilection for dorsocervical fat accumulation reflects the high local expression of 11β-HSD1 and glucocorticoid receptors in this depot. Additionally, the cervical adipose tissue appears particularly sensitive to the lipogenic effects of insulin, which is typically elevated in hypercortisolemic states due to cortisol-induced insulin resistance. This creates a perfect storm for fat accumulation: high local cortisol activation combined with systemic hyperinsulinemia.

Differentiating Dorsocervical Fat Pad from Simple Obesity

The critical challenge facing the internist is distinguishing pathologic ectopic fat accumulation from benign obesity. While obesity is epidemic, affecting over 40% of adults in many developed nations, Cushing's syndrome remains rare. Yet the consequences of missing Cushing's syndrome are severe: uncontrolled hypertension, diabetes, devastating infections, osteoporotic fractures, and psychological morbidity.

Key Distinguishing Features

1. The Pattern of Fat Distribution

Simple obesity typically shows generalized fat accumulation with preservation of normal body proportions. The obese patient may have a full posterior neck, but this occurs in the context of generalized subcutaneous fat throughout the body. In contrast, Cushing's syndrome produces redistribution—central accumulation with peripheral depletion.

The Supraclavicular Fat Diagnostic Hack: Perhaps the single most discriminating physical finding is supraclavicular fat pad fullness. In a landmark study by Rockall and colleagues, supraclavicular fat pad thickness >2 cm on CT imaging demonstrated 95% sensitivity for Cushing's syndrome when combined with increased visceral fat. On physical examination, the inability to palpate the clavicle easily due to supraclavicular fullness is highly suggestive. Simple obesity rarely produces this finding.

Clinical Examination Technique: Have the patient sit upright with shoulders relaxed. Palpate the supraclavicular fossae bilaterally. In normal individuals or simple obesity, you should easily palpate the clavicle with a shallow fossa above it. In Cushing's syndrome, the fossae are filled or convex, and the clavicle is difficult to palpate.

2. Associated Stigmata

The presence of other Cushing's features dramatically increases specificity:

• Wide (>1 cm) purple striae: Present in 50-70% of Cushing's cases; the purple color reflects the thinned dermis allowing visualization of underlying vasculature
• Easy bruising and skin fragility: Reported by 65% of patients
• Proximal myopathy: Difficulty rising from a chair without using arms is present in 60-80%
• Thin skin: Particularly evident on the dorsum of hands
• Facial plethora: Beyond simple ruddiness, representing true telangiectasia

Oyster: The absence of striae does NOT exclude Cushing's syndrome, particularly in older adults where skin loses elasticity and may not develop striae despite rapid weight changes.

3. The Temporal Pattern

Simple obesity typically develops gradually over years. Cushing's syndrome often presents with relatively rapid weight gain and redistribution over 6-18 months. Obtaining old photographs is invaluable—patients may not recognize gradual changes, but photographic evidence of rapid facial rounding and dorsocervical fat accumulation over 12 months is highly suggestive.

The "Moon Facies" Plus Ectopic Fat Combination: A Pathognomonic Pairing

When moon facies occurs in conjunction with dorsocervical and supraclavicular fat pads, the specificity for hypercortisolism approaches 95%. Moon facies results from increased facial adipose tissue combined with fluid retention. The face appears round, full, and convex, with loss of normal contours and obliteration of the zygomatic arch prominence.

The Combined Sign: A patient presenting with the triad of moon facies, dorsocervical fat pad, and supraclavicular fullness should be considered to have Cushing's syndrome until proven otherwise. This combination is rarely seen in simple obesity because generalized weight gain preserves relative facial contours.

Photographic Documentation

In the modern era, smartphones provide an invaluable diagnostic tool. Request the patient to show photographs from 1-2 years prior. The change is often shocking when compared side-by-side. Document this with medical photography at baseline to track treatment response.

Clinical Hack: Create a side-by-side comparison using the patient's old driver's license or passport photo alongside a current photo taken in the same lighting and angle. This visual evidence often convinces skeptical patients of the need for extensive workup.

HIV-Related Lipodystrophy: The Critical Modern Mimic

The differential diagnosis of dorsocervical fat pad was revolutionized by the HIV epidemic and subsequent introduction of antiretroviral therapy (ART). HIV-associated lipodystrophy syndrome (HALS) can produce a buffalo hump that is clinically indistinguishable from Cushing's syndrome on inspection alone.

Pathophysiology of HALS

Lipodystrophy in HIV affects 30-50% of patients on ART, though rates have decreased with newer regimens. The syndrome involves:

• Peripheral lipoatrophy: Loss of subcutaneous fat in face, limbs, and buttocks
• Central lipohypertrophy: Accumulation of dorsocervical, visceral, and breast fat

The mechanisms are multifactorial. Early protease inhibitors (PIs) interfered with adipocyte differentiation and triggered apoptosis of subcutaneous adipocytes. Nucleoside reverse transcriptase inhibitors (NRTIs), particularly stavudine and zidovudine, caused mitochondrial toxicity in adipocytes. Modern regimens, especially integrase inhibitors, carry substantially lower risk, but lipodystrophy persists in many long-term survivors initiated on older regimens.

Clinical Differentiation from Cushing's Syndrome

History is paramount:

• HIV status: Known HIV infection and ART use, particularly older regimens
• Temporal relationship: Lipodystrophy typically develops 1-2 years after ART initiation
• Associated features: HALS patients often have prominent facial lipoatrophy with sunken cheeks and temporal wasting—the opposite of Cushing's moon facies

Biochemical Clues:

• Insulin resistance and dyslipidemia are common to both conditions
• Hypercortisolism markers (see below) are absent in HALS
• Elevated triglycerides (often >500 mg/dL) with low HDL are characteristic of HALS

Physical Examination Distinctions:

Feature	Cushing's Syndrome	HIV Lipodystrophy
Facial fat	Moon facies	Facial lipoatrophy
Extremity fat	Preserved or slightly reduced	Marked lipoatrophy
Striae	Common (purple, wide)	Absent
Skin changes	Thin, fragile, easy bruising	Normal
Proximal myopathy	Present	Absent
Dorsocervical fat	Present	Present

Pearl: The combination of dorsocervical fat with facial lipoatrophy is characteristic of HIV lipodystrophy, not Cushing's syndrome. When these occur together, check HIV status before embarking on a Cushing's workup.

Other Causes in the Differential Diagnosis

Exogenous Glucocorticoid Administration

Iatrogenic Cushing's syndrome from prescribed corticosteroids is far more common than endogenous disease. Any patient on prednisone ≥7.5 mg daily (or equivalent) for >3 months can develop cushingoid features. The clinical picture is identical to endogenous Cushing's syndrome.

The Hidden Glucocorticoids: Don't forget to ask about:

• Inhaled corticosteroids in high doses
• Topical steroids applied to large body surface areas
• Intra-articular injections (particularly depot preparations)
• Ritonavir-boosted regimens (ritonavir inhibits cortisol metabolism, potentiating any steroid exposure)

Polycystic Ovary Syndrome (PCOS)

PCOS can produce some central obesity and occasionally mild dorsocervical fullness, but the degree is much less pronounced than in Cushing's syndrome. The presence of hirsutism, irregular menses, and polycystic ovaries on ultrasound suggests PCOS. However, Cushing's syndrome can also cause hirsutism and menstrual irregularity, so distinguishing features (striae, skin fragility, profound proximal myopathy) must be sought.

Obesity with Insulin Resistance (Metabolic Syndrome)

Severe insulin resistance can produce some central fat accumulation but should not produce supraclavicular fullness or the dramatic redistribution pattern of Cushing's syndrome. When in doubt, screen for hypercortisolism.

Madelung's Disease (Benign Symmetric Lipomatosis)

This rare condition produces symmetric fatty masses around the neck, shoulders, and upper trunk, creating a "horse collar" appearance. It typically occurs in middle-aged men with significant alcohol use. The masses are soft, non-tender lipomas that can be distinguished from Cushing's by the symmetric collar-like distribution and absence of other cushingoid features.

Initiating the Cushing's Syndrome Workup

When clinical suspicion for Cushing's syndrome is raised, the next step is biochemical confirmation of hypercortisolism. The Endocrine Society guidelines recommend initial screening with one or more of the following tests:

First-Line Screening Tests

1. 24-Hour Urinary Free Cortisol (UFC)

The 24-hour UFC measures integrated cortisol production over a full day. Normal values are <50 mcg/24 hours (138 nmol/24 hours) by most assays, though this varies by laboratory. Values >4 times the upper limit of normal are virtually diagnostic of Cushing's syndrome in the appropriate clinical context.

Technical Considerations:

• Ensure complete collection (check urinary creatinine: should be 15-20 mg/kg ideal body weight in men, 10-15 mg/kg in women)
• False positives occur with high fluid intake (>5 L/day), causing cortisol dilution below assay sensitivity
• Avoid collection during acute illness, which can physiologically elevate cortisol
• Consider obtaining 2-3 collections, as sensitivity improves with multiple samples

The Diagnostic Hack: Provide the patient with written instructions and a 24-hour collection container. Have them practice the collection process: start collection after discarding the first morning void, then collect all urine for exactly 24 hours including the first morning void the next day. Incomplete collections are the most common reason for false-negative results.

2. Late-Night Salivary Cortisol

This test exploits the loss of normal circadian cortisol rhythm in Cushing's syndrome. Healthy individuals show cortisol nadir between 11 PM and midnight. Cushing's patients maintain elevated late-night cortisol levels.

Advantages:

• Convenient outpatient collection
• Not affected by cortisol-binding globulin variations (measures free cortisol)
• Can be repeated easily
• Excellent sensitivity (95-100%) and specificity (90-95%)

Collection Technique:

• Collect saliva sample between 11 PM and midnight
• Patient should be in their home environment (hospitalized patients may have physiologically elevated cortisol)
• Avoid eating, drinking, or brushing teeth for 30 minutes before collection
• Sample can be frozen and brought to lab later
• Normal values: <100 ng/dL (2.8 nmol/L), though this varies by assay

Pearl: Obtain two samples on different nights. A single elevated value may reflect stress, but two elevated samples have >95% specificity for Cushing's syndrome.

3. Low-Dose Dexamethasone Suppression Test (LDDST)

The 1-mg overnight dexamethasone suppression test assesses the ability of exogenous glucocorticoid to suppress endogenous cortisol production. In healthy individuals, even a small dose of dexamethasone suppresses ACTH and cortisol. In Cushing's syndrome, this feedback is impaired.

Protocol:

• Administer 1 mg dexamethasone orally at 11 PM
• Measure serum cortisol at 8 AM the following morning
• Suppression to <1.8 mcg/dL (50 nmol/L) excludes Cushing's syndrome with high sensitivity

False Positives:

• Rapid dexamethasone metabolism (enzyme inducers: phenytoin, rifampin, phenobarbital)
• Stress, depression, or severe obesity
• Elevated cortisol-binding globulin (pregnancy, estrogen use)

Oyster: The dexamethasone suppression test has lower specificity than UFC or late-night salivary cortisol, particularly in obese patients. Use it as part of a panel rather than in isolation.

Practical Approach to Screening

For patients with high clinical suspicion (buffalo hump + moon facies + proximal myopathy), I recommend:

Screening Panel:

1. Two 24-hour urinary free cortisol collections
2. Two late-night salivary cortisol samples
3. 1-mg overnight dexamethasone suppression test

If any two of these three tests are abnormal, the diagnosis of Cushing's syndrome is established, and the patient should be referred to endocrinology for further workup to determine the etiology (pituitary adenoma, ectopic ACTH, or adrenal tumor).

The Outpatient Workup Strategy:

• Order the screening panel at the initial visit
• Provide detailed written instructions for all collections
• Schedule a follow-up appointment in 2-3 weeks to review results
• If positive, obtain morning ACTH level before the follow-up visit
• Refer to endocrinology for definitive localization studies (pituitary MRI, high-dose dexamethasone suppression test, inferior petrosal sinus sampling if needed)

Conclusion

The dorsocervical fat pad, while a striking physical finding, requires the astute internist to integrate historical, clinical, and biochemical data to reach the correct diagnosis. The key is recognizing patterns: the redistribution pattern and associated stigmata that distinguish Cushing's syndrome from simple obesity, and the facial lipoatrophy that points toward HIV lipodystrophy rather than hypercortisolism.

When doubt exists, screen for hypercortisolism. The tests are relatively inexpensive, and the cost of missing Cushing's syndrome—in terms of morbidity, mortality, and healthcare utilization—is substantial. With modern screening tests, particularly late-night salivary cortisol, we can efficiently identify patients who require subspecialty evaluation while sparing the majority of obese patients from unnecessary testing.

The buffalo hump remains a powerful visual diagnosis, a physical sign that, when properly interpreted, provides immediate insight into underlying pathophysiology and guides focused investigation. Master this sign, and you master an essential skill in clinical endocrinology.

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