Acral Changes in Acromegaly: The Art of Clinical Observation in Internal Medicine

A Review Article for Postgraduate Physicians

Dr Neeraj Manikath ,claude.ai

Abstract

Acromegaly remains one of the most visually striking yet frequently delayed diagnoses in internal medicine, with an average diagnostic lag of 7-10 years from symptom onset. The insidious progression of acral changes—spade-like hands, coarse facial features, and soft tissue overgrowth—challenges the astute clinician to recognize patterns that patients themselves often fail to notice. This review emphasizes the critical role of physical examination in identifying acromegaly, explores practical bedside techniques including the "ring test" and "old photo sign," discusses optimal screening strategies, and differentiates acromegaly from important clinical mimics. Mastering these observational skills represents a cornerstone of excellence in internal medicine practice.

Introduction: The Silent Metamorphosis

Acromegaly, derived from the Greek words "akros" (extremity) and "megas" (large), results from chronic growth hormone (GH) excess, most commonly from a pituitary adenoma. With an estimated prevalence of 60-70 cases per million and an incidence of 3-4 cases per million annually, this rare condition demands diagnostic vigilance. The gradual nature of physical changes—occurring over years—creates a paradox: the alterations are profound yet invisible to both patient and family who observe them daily. This phenomenon, akin to watching a child grow, underscores why acromegaly diagnosis requires the trained eye of a physician who deliberately looks for subtle signs.

The morbidity associated with untreated acromegaly is substantial. Patients face increased cardiovascular mortality, with a two to four-fold elevation in standardized mortality ratio, predominantly from cardiomyopathy and arrhythmias. Additionally, the risks of colorectal neoplasia, sleep apnea, arthropathy, and metabolic complications including diabetes mellitus significantly impair quality of life. Early diagnosis through careful physical examination can dramatically alter outcomes, making the recognition of acral changes a high-value clinical skill.

The "Ring Test": A Simple Yet Profound Observation

Historical Perspective and Clinical Utility

One of the most practical bedside assessments for suspected acromegaly involves the seemingly mundane observation of ring fit. The "ring test" capitalizes on the patient's own baseline—their wedding band or other long-worn jewelry serves as an internal control spanning years or decades.

How to Perform the Ring Test:

During history-taking, inquire: "Have you noticed any changes in your ring size? Can you still wear your wedding ring?"
If the patient reports difficulty, ask: "When did you last wear it comfortably?"
Request to see old rings or photographs showing hands with jewelry
Document ring size changes if quantifiable (many patients remember going from size 6 to 8 or 9)

The pathophysiology underlying this sign involves soft tissue proliferation and bone expansion. Growth hormone stimulates insulin-like growth factor-1 (IGF-1) production in the liver, which drives chondrocyte proliferation in cartilage, increased hyaluronic acid deposition in soft tissues, and periosteal bone growth. The fingers become not only longer but also broader, with characteristic spade-like appearance due to tuft expansion of the distal phalanges.

Clinical Pearl: A patient who has progressively purchased larger rings over 5-10 years has essentially documented their disease progression. This represents objective evidence more reliable than subjective reporting of "swollen hands."

Sensitivity and Specificity Considerations

While no formal studies have validated the sensitivity of the ring test, clinical experience suggests it identifies approximately 70-80% of patients with established acromegaly. False negatives occur in:

Early disease where soft tissue changes are minimal
Patients who never wore rings
Those with concurrent inflammatory arthropathy causing joint swelling

Conversely, other conditions causing ring tightness include weight gain with peripheral edema, inflammatory arthritis, pregnancy, and hypothyroidism. Thus, the ring test serves as a screening observation rather than a diagnostic criterion, prompting further evaluation when positive.

The "Old Photo" Sign: Visual Documentation of Disease Progression

The Power of Photographic Evidence

Perhaps no single diagnostic maneuver rivals the impact of comparing current facial appearance with photographs from 5, 10, or 20 years prior. The "old photo sign" transforms subtle, gradual changes into striking visual evidence.

Implementing the Old Photo Sign in Practice:

Request the patient bring a driver's license, passport, or old identification photographs
Compare these with current appearance, focusing on:
- Frontal bone bossing
- Supraorbital ridge prominence
- Nose enlargement (both length and width)
- Lip thickness, particularly lower lip
- Jaw protrusion (prognathism)
- Overall facial coarsening
Family albums or wedding photos provide additional temporal data points
Document findings with photography if consent obtained

The gradual facial metamorphosis in acromegaly reflects both bone and soft tissue changes. Increased growth hormone leads to mandibular enlargement (prognathism), maxillary widening, frontal sinus expansion creating brow prominence, and soft tissue thickening of the nose, lips, and ears. These changes occur so slowly that even spouses may not recognize them until photographic comparison makes them evident.

Teaching Point for Residents: Show patients their old photos during the clinical encounter. The moment of recognition—when patients see their own transformation—often converts diagnostic suspicion into motivated participation in workup. This technique also demonstrates empathy, as you help patients understand changes they may have attributed to "normal aging."

Evidence from Literature

A landmark study by Nachtigall and colleagues demonstrated that even experienced endocrinologists could identify acromegaly from facial photographs with high accuracy when comparing serial images. The diagnostic accuracy improved from 65% with single current photos to over 85% when temporal comparison was possible, validating this clinical approach.

Beyond the Hands: The Complete Physical Examination

Macroglossia: An Often Overlooked Finding

Tongue enlargement represents one of the most specific yet underappreciated signs of acromegaly. The tongue grows due to muscular hypertrophy and can lead to several clinical consequences:

Obstructive sleep apnea: Present in 60-80% of acromegaly patients
Dental impressions: Lateral tongue scalloping from teeth pressure
Speech changes: Patients may develop deeper voice and articulation difficulties
Mask fit problems: Relevant for CPAP therapy

Bedside Assessment: Ask the patient to protrude their tongue. A macroglossia tongue will appear disproportionately large, may not fit comfortably in the mouth when relaxed, and shows lateral indentations from dental pressure. Comparing tongue size to mouth opening provides a rough quantitative assessment.

Prognathism and Dental Changes

Mandibular overgrowth creates the characteristic jutting jaw of acromegaly. This produces several observable changes:

Malocclusion: The lower teeth protrude beyond the upper teeth (Class III malocclusion)
Increased interdental spacing: Termed diastema, this results from jaw widening exceeding tooth growth
Temporomandibular joint dysfunction: Many patients report jaw pain or clicking

Clinical Hack: Ask the patient to bite down naturally and observe the alignment. In normal occlusion, upper incisors slightly overlap lower incisors. In acromegaly-associated prognathism, this relationship reverses. Also inquire about dental work—patients often report needing dental bridges or implants due to spacing changes.

Additional Soft Tissue Findings

A comprehensive examination reveals:

Skin tags: Present in up to 50% of patients, particularly in axillae and neck
Increased heel pad thickness: Can be measured on lateral foot X-ray (>23mm in males, >21.5mm in females suggests acromegaly)
Husky, deep voice: From laryngeal soft tissue hypertrophy and vocal cord thickening
Excessive sweating and oily skin: Due to increased sweat and sebaceous gland activity

Oyster: The combination of skin tags, acanthosis nigricans, and metabolic syndrome should prompt IGF-1 screening, as growth hormone excess creates insulin resistance and hyperinsulinemia, manifesting as these cutaneous findings.

The "Not So Simple" Screening: Why IGF-1 Trumps Random Growth Hormone

Understanding Growth Hormone Physiology

Growth hormone secretion is pulsatile, with approximately 8-10 secretory bursts daily, primarily during deep sleep. Factors influencing GH secretion include:

Stimulatory: Sleep, exercise, stress, hypoglycemia, amino acids
Inhibitory: Hyperglycemia, elevated free fatty acids, glucocorticoids

This physiologic variability renders random GH measurements nearly useless for diagnosing acromegaly. A single elevated GH level may reflect normal pulsatile secretion, while a single normal value doesn't exclude acromegaly (the trough between pulses).

IGF-1: The Superior Screening Test

Insulin-like growth factor-1 (IGF-1), also called somatomedin C, is produced primarily by hepatocytes in response to growth hormone stimulation. Unlike GH, IGF-1 has a long half-life (approximately 12-15 hours) and stable circulating levels throughout the day, making it ideal for screening.

Advantages of IGF-1:

Integrated marker: Reflects 24-hour GH secretion
Stable levels: Single random sample suffices
Age-adjusted normative data: Allows comparison to age-appropriate controls
High sensitivity: Elevated in >95% of active acromegaly cases

Critical Interpretation Points:

Must use age-adjusted reference ranges (IGF-1 declines with age)
Severe malnutrition, liver disease, and poorly controlled diabetes can falsely lower IGF-1
Pregnancy and estrogen therapy elevate IGF-1 binding proteins, potentially lowering free IGF-1 and causing false negatives

Diagnostic Algorithm:

Suspect acromegaly based on clinical features → Order IGF-1
If IGF-1 elevated → Perform oral glucose tolerance test (OGTT) with GH measurements
Normal subjects suppress GH to <1 ng/mL (or <0.4 ng/mL with ultrasensitive assays) during OGTT
Acromegaly patients fail to suppress GH adequately
If biochemically confirmed → Pituitary MRI to locate adenoma

Pearl for Practice: Never order a random GH as initial screening. The mantra should be: "Suspect acromegaly? Think IGF-1 first." Random GH testing wastes resources and confuses clinical picture, as both false positives and false negatives are common.

Mimics to Consider: Avoiding Diagnostic Pitfalls

Pachydermoperiostosis (Primary Hypertrophic Osteoarthropathy)

This rare hereditary disorder, also called Touraine-Solente-Golé syndrome, can mimic acromegaly through its presentation of:

Thickened facial skin with deep furrows and folds (cutis verticis gyrata)
Digital clubbing and periosteal new bone formation
Enlarged hands and feet
Hyperhidrosis and seborrhea

Differentiating Features:

Age of onset: Pachydermoperiostosis typically manifests during adolescence, whereas acromegaly presents in the third to fourth decade
Family history: Autosomal dominant or recessive inheritance in pachydermoperiostosis
Radiographic findings: Periosteal thickening along long bone shafts in pachydermoperiostosis vs. enlarged pituitary fossa in acromegaly
Laboratory: Normal IGF-1 in pachydermoperiostosis
Clubbing: More prominent in pachydermoperiostosis; uncommon in acromegaly

Clinical Hack: Look at the fingertips. Severe clubbing with Lovibond angle loss suggests pachydermoperiostosis or secondary hypertrophic osteoarthropathy (malignancy, pulmonary disease). Acromegaly produces spade-like fingers with enlarged tufts but typically preserves the nail-fold angle.

Severe Hypothyroidism in Infancy (Cretinism)

While modern newborn screening has made untreated congenital hypothyroidism rare in developed nations, it remains diagnostically relevant in:

Regions without universal screening
Patients from resource-limited countries
Historical case discussions

Features of Cretinism Overlapping with Acromegaly:

Coarse facial features
Macroglossia
Thickened skin
Broad hands

Distinguishing Features:

Intellectual disability: Present in untreated cretinism, absent in acromegaly
Growth retardation: Severe short stature in cretinism vs. overgrowth in acromegaly
Thyroid function tests: Diagnostic
Age of onset: Infantile for cretinism vs. adult for acromegaly
Prognathism: Not a feature of hypothyroidism

Teaching Moment: When evaluating coarse features in an adult immigrant patient with unclear medical history, consider both current thyroid function and whether childhood hypothyroidism was untreated. The constellation of short stature, developmental delay, and coarse features points to cretinism, not acromegaly.

Other Conditions to Consider

Myxedema (Adult Hypothyroidism):

Facial puffiness and coarse features
Macroglossia possible but less prominent
Cold intolerance, weight gain, bradycardia distinguish from acromegaly
Thyroid testing confirms diagnosis

McCune-Albright Syndrome:

Café-au-lait spots
Polyostotic fibrous dysplasia
Precocious puberty
Can have GH excess but distinguishable by age of onset and associated features

Neurofibromatosis Type 1:

Facial plexiform neurofibromas can create facial asymmetry and coarsening
Café-au-lait macules and axillary freckling
Optic pathway gliomas may affect pituitary region but don't cause true acromegaly

Clinical Pearls and Diagnostic Hacks

Pearl 1: The "Glove Size" Inquiry

Ask male patients about glove size progression. Men who wore size medium gloves progressing to large or extra-large provide objective longitudinal data. Similarly, shoe size increases of 1-2 sizes in adults warrant investigation.

Pearl 2: The Obstructive Sleep Apnea Connection

Any patient with severe OSA requiring high CPAP pressures (>15 cm H2O) and refractory to standard therapy should undergo acromegaly screening. The prevalence of OSA in acromegaly reaches 80%, and treatment of the underlying acromegaly often improves or resolves sleep-disordered breathing.

Pearl 3: The "Headache + Amenorrhea" Presentation

Young women with oligomenorrhea or amenorrhea plus headaches often receive extensive gynecologic workup. Adding the observation of coarse features or acral enlargement should immediately redirect attention to pituitary pathology, as macroadenomas causing acromegaly frequently compress normal pituitary tissue, causing secondary hypogonadism.

Hack 1: The Smartphone Photo Archive

Modern patients carry years of dated photographs on smartphones. During consultation, ask patients to scroll through their photo library showing pictures from 3, 5, and 10 years prior. This real-time comparison during the visit can be diagnostically revelatory.

Hack 2: The Grip Strength Test

While not specific, markedly increased grip strength (easily overpowering the examiner's hand) combined with large hands suggests acromegaly. GH excess increases muscle mass and bone size, translating to increased strength beyond what obesity or athletic conditioning would produce.

Oyster 1: Acromegaly and Colonic Polyps

Patients with acromegaly have 2-3 times increased risk of colonic adenomas and adenocarcinoma. Once diagnosed, colonoscopic surveillance should begin regardless of age, with follow-up intervals determined by findings. This association likely reflects IGF-1's proliferative effects on colonic epithelium.

Oyster 2: The Cardiac Connection

Acromegalic cardiomyopathy represents a specific entity characterized by biventricular hypertrophy, diastolic dysfunction progressing to systolic dysfunction, and eventual heart failure. Any patient with unexplained cardiomyopathy and subtle acral changes warrants IGF-1 screening. Early treatment can reverse cardiac changes if intervention occurs before fibrosis develops.

Conclusion: Elevating Observational Medicine

The diagnosis of acromegaly through recognition of acral changes represents clinical medicine at its finest—synthesizing history, physical examination, pattern recognition, and confirmatory testing into actionable diagnosis. The "ring test" and "old photo sign" embody low-tech, high-yield clinical reasoning that no algorithm or laboratory panel can replace.

For the internist-in-training, mastering these observational skills transcends acromegaly diagnosis. The same deliberate, systematic approach—looking not just at the patient but truly seeing them—applies across internal medicine. Whether recognizing the subtle ptosis of myasthenia gravis, the malar rash of systemic lupus erythematosus, or the xanthomas of familial hypercholesterolemia, excellence demands cultivation of the clinical eye.

The average 7-10 year diagnostic delay in acromegaly is not inevitable. Every physician who examines a patient with this condition has the opportunity to be the one who notices what others have missed. Armed with knowledge of what to look for, simple bedside tests like the ring fit and photo comparison, and understanding of appropriate biochemical screening with IGF-1, we can compress this delay, reduce morbidity, and demonstrate the enduring value of the physical examination.

The art of observation in medicine requires practice, teaching, and conscious attention. By incorporating these techniques into routine practice and teaching them to successive generations of physicians, we honor the fundamental truth that sophisticated diagnosis often begins with simply opening our eyes.

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