Hair Loss & Skin Changes: The Derm-Endocrine Overlap

A Practical Clinical Review for Internal Medicine Postgraduates

Dr Neeraj Manikath , claude.ai

Abstract: Cutaneous manifestations of endocrine disorders represent a critical diagnostic frontier where astute clinical observation can lead to early detection of systemic disease. This review synthesizes current evidence on the dermatologic presentations of common endocrine pathologies, emphasizing pattern recognition that enables rapid clinical diagnosis. The integration of dermatologic and endocrinologic assessment provides immediate practical value in outpatient settings where these presentations constitute a significant source of patient distress and diagnostic opportunity.

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Introduction

The skin and its appendages serve as accessible windows into systemic endocrine function. Hair loss and skin changes frequently represent the presenting complaint that brings patients to medical attention, often preceding laboratory confirmation of endocrine dysfunction by months or years. For the internist, mastery of these visible signs transforms the physical examination into a powerful diagnostic tool, enabling targeted investigation and early intervention.

The emotional impact of visible changes cannot be understated. Hair loss, in particular, generates profound psychological distress disproportionate to its medical significance, making prompt recognition and management a therapeutic imperative. This review focuses on high-yield clinical patterns that bridge dermatology and endocrinology, equipping the practicing physician with immediately applicable diagnostic skills.

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The Pattern of Loss Matters: Diffuse vs. Androgenic Alopecia

Clinical Pearl: Hair Distribution Tells the Story

Hair loss patterns provide crucial diagnostic clues before any laboratory test is ordered. The systematic assessment of hair loss distribution should be the first step in every evaluation.

Diffuse Hair Loss (Telogen Effluvium Pattern): The hallmark of thyroid disease and nutritional deficiencies is generalized thinning without focal areas of complete baldness. In telogen effluvium secondary to hypothyroidism or iron deficiency, approximately 30-50% of scalp hair shifts prematurely into the telogen (resting) phase, resulting in diffuse shedding 2-4 months after the triggering event.(1,2)

Clinical Hack: The "hair pull test" remains underutilized. Gently grasp 50-60 hairs between thumb and forefinger and pull with mild traction. In active telogen effluvium, more than 6 hairs (>10%) will be extracted easily, with visible white bulbs at the root indicating telogen-phase follicles.(3)

Androgenic Pattern: In contrast, polycystic ovary syndrome (PCOS) and hyperandrogenism produce the classic male-pattern baldness distribution even in women: bitemporal recession and vertex thinning with preservation of the occipital region. This distribution reflects the androgen sensitivity of frontal and vertex follicles compared to androgen-independent occipital follicles.(4)

Diagnostic Oyster: Young women presenting with male-pattern hair loss warrant investigation for hyperandrogenism even in the absence of hirsutism or menstrual irregularity. Free testosterone, DHEA-S, and 17-hydroxyprogesterone levels should be assessed to exclude ovarian or adrenal sources.(5)

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Thyroid Hair & Skin: The Classic Triad

Hypothyroidism: Brittle, Coarse, and Dry

Thyroid hormone regulates keratinocyte proliferation, sebaceous gland function, and hair follicle cycling. Hypothyroidism produces a constellation of changes recognizable at the bedside:

Hair Changes:

• Texture alteration: Hair becomes coarse, dry, and brittle due to decreased hair shaft water content and altered keratin cross-linking
• The pathognomonic "Queen Anne sign": Loss of the lateral third of eyebrows (madarosis), present in up to 30% of hypothyroid patients(6)
• Diffuse thinning: Affects scalp, axillary, and pubic hair due to prolonged telogen phase

Skin Manifestations:

• Xerosis: Dry, cool, rough skin reflecting decreased sweating and sebum production
• Carotenemia: Yellow-orange discoloration of palms and soles (sparing sclera) from impaired hepatic conversion of carotene to vitamin A(7)
• Myxedema: Non-pitting periorbital and pretibial edema from dermal mucopolysaccharide deposition

Clinical Pearl: The skin temperature difference is palpable. In a warm examination room, the hypothyroid patient's extremities feel distinctly cool compared to normal subjects—a finding that predates thermometry by centuries.

Hyperthyroidism: Warm, Moist, and Fragile

The hypermetabolic state produces opposite changes:

• Warm, moist, velvety skin with increased sweating
• Fine, soft, fragile hair with accelerated growth and premature telogen phase
• Pretibial myxedema (in Graves' disease specifically): Waxy, infiltrated plaques on anterior tibias from glycosaminoglycan deposition, seen in 1-5% of Graves' patients(8)

Don't Miss: Thyroid acropachy (digital clubbing with periosteal new bone formation) accompanies pretibial myxedema in severe Graves' disease and indicates high autoantibody titers requiring aggressive management.(9)

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Hyperandrogenism Signs: The PCOS Phenotype

The Clinical Triad: Hirsutism, Acne, and Androgenic Alopecia

PCOS affects 6-12% of reproductive-age women and represents the most common endocrine disorder in this population.(10) Its cutaneous manifestations create the visible phenotype that drives many patients to seek care.

Hirsutism Evaluation: Terminal (coarse, pigmented) hair growth in male-pattern distribution affects 70-80% of women with PCOS. The modified Ferriman-Gallwey score objectively quantifies hirsutism across nine body areas, with scores >8 indicating hyperandrogenism in most populations.(11)

Clinical Hack: Focus assessment on the "highest-yield" areas: chin, upper lip, chest (periareolar), and lower abdomen (linea alba). These sites demonstrate earlier and more pronounced changes than limbs.

Acne Beyond Adolescence: Post-adolescent acne, particularly when distributed along the jawline and neck, suggests hyperandrogenism until proven otherwise. This distribution differs from typical adolescent acne, which predominates in the T-zone.(12)

Acanthosis Nigricans: The Insulin Resistance Herald

Acanthosis nigricans (AN) deserves special emphasis as a critical clinical marker that transcends cosmetic concern. This velvety, hyperpigmented, papillomatous thickening affects intertriginous areas: posterior neck, axillae, groin, and inframammary folds.

Pathophysiology: Hyperinsulinemia stimulates insulin-like growth factor-1 (IGF-1) receptors on keratinocytes and fibroblasts, promoting proliferation. The condition indicates severe insulin resistance, with fasting insulin levels often exceeding 20-30 μIU/mL.(13)

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The Acanthosis Nigricans Action Plan: Beyond the Skin Finding

A Roadmap for Systematic Evaluation

When AN is identified, a structured approach is essential:

Immediate Assessment:

1. Exclude malignancy: Rapid-onset, extensive AN in patients >40 years may indicate internal malignancy (gastric adenocarcinoma most common). This "malignant acanthosis nigricans" requires urgent investigation.(14)
2. Document extent: Photograph and measure involvement to track treatment response
3. Screen for metabolic syndrome: Check fasting glucose, HbA1c, lipid panel, and blood pressure

Metabolic Investigation:

• Oral glucose tolerance test (OGTT): More sensitive than fasting glucose for detecting prediabetes in this population
• HOMA-IR calculation: [Fasting insulin (μIU/mL) × fasting glucose (mg/dL)] / 405; values >2.5 indicate insulin resistance(15)
• Screen for PCOS: If premenopausal woman, assess menstrual history, perform pelvic ultrasound, and measure androgens

Therapeutic Framework: The presence of AN mandates aggressive lifestyle intervention and often pharmacotherapy:

• Weight reduction: 5-10% weight loss improves insulin sensitivity and can reverse AN
• Metformin: Indicated for prediabetes/diabetes with documented insulin resistance; dosing 1500-2000 mg daily(16)
• Topical agents: Tretinoin 0.05-0.1% cream and ammonium lactate 12% lotion improve cosmesis but do not address underlying pathology

Clinical Oyster: AN in normal-weight individuals should prompt investigation for lipodystrophy syndromes, familial partial lipodystrophy, or monogenic insulin resistance disorders—rare but important diagnoses.(17)

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The "Don't Miss" Skin Findings: High-Stakes Diagnoses

Hyperpigmentation in Addison's Disease: The ACTH Effect

Primary adrenal insufficiency produces distinctive hyperpigmentation from elevated ACTH and melanocyte-stimulating hormone (MSH), which share a common precursor molecule (pro-opiomelanocortin).(18)

Distribution Pattern:

• Sun-exposed areas: Face, neck, dorsal hands
• Friction areas: Elbows, knees, belt line, bra straps
• Oral mucosa: Buccal mucosa, gingival margins (pathognomonic when present)
• Palmar creases: Accentuated pigmentation in natural creases
• Scars: Hyperpigmented scars acquired after disease onset

Clinical Pearl: Compare the patient's palmar creases to your own. In Addison's disease, their creases will be noticeably darker—a finding that costs nothing but provides diagnostic gold.

Diagnostic Pitfall: Early Addison's disease may present with subtle hyperpigmentation dismissed as "sun tan" or attributed to ethnic background. Maintain high suspicion in patients with fatigue, weight loss, and orthostatic hypotension.

Pretibial Myxedema in Graves' Disease: The Autoimmune Marker

Despite its name, pretibial myxedema occurs in hyperthyroidism (Graves' disease specifically), not hypothyroidism. This thyroid dermopathy results from stimulation of fibroblasts by thyroid-stimulating immunoglobulins (TSI), causing glycosaminoglycan accumulation.(19)

Clinical Features:

• Location: Anterior lower legs (90%), occasionally dorsal feet and hands
• Appearance: Waxy, indurated, non-pitting plaques with prominent hair follicles ("orange peel" texture)
• Association: Nearly always accompanied by Graves' ophthalmopathy; suggests severe disease

Management Implications: Presence of pretibial myxedema indicates:

1. High TSI titers requiring aggressive treatment
2. Increased risk of treatment-refractory disease
3. Need for ophthalmology consultation (90% have eye involvement)(20)

Topical high-potency corticosteroids under occlusion provide symptomatic relief but do not alter disease course. Definitive management requires achieving euthyroidism.

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Practical Integration: Building a Systematic Approach

The 60-Second Derm-Endocrine Screen

In busy clinical practice, a focused examination can be completed rapidly:

1. Hair: Assess distribution (diffuse vs. patterned), texture (fine vs. coarse), lateral eyebrows (present vs. absent)
2. Face: Note acne distribution, hirsutism (chin/upper lip), and general pigmentation
3. Neck: Inspect posterior neck for AN and general pigmentation
4. Hands: Examine palmar creases for hyperpigmentation, note skin texture and temperature
5. Lower legs: Inspect anterior tibias for myxedema or infiltrative changes

Laboratory Strategy: Targeted, Not Shotgun

Based on clinical findings, pursue directed testing:

For Hair Loss:

• Diffuse pattern: TSH, free T4, ferritin, complete blood count
• Androgenic pattern: Total/free testosterone, DHEA-S, 17-hydroxyprogesterone

For Acanthosis Nigricans:

• Fasting glucose and insulin, HbA1c
• Lipid panel
• If PCOS suspected: LH, FSH, androgens, pelvic ultrasound

For Hyperpigmentation:

• AM cortisol and ACTH
• If low: Cosyntropin stimulation test
• Electrolytes (hyponatremia, hyperkalemia suggest Addison's)

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Pearls for Practice

1. The Eyebrow Sign: Loss of lateral eyebrows (Queen Anne sign) has 75% specificity for hypothyroidism when present, but only 30% sensitivity—absence does not exclude the diagnosis.(21)

2. The Ferritin Threshold: Hair loss evaluation requires ferritin >40 ng/mL for optimal hair growth; many laboratories report "normal" at >15 ng/mL, leading to missed diagnoses.(22)

3. The PCOS Paradox: Up to 30% of women with hyperandrogenic PCOS have normal-range testosterone levels on random testing. Early morning (before 10 AM) sampling and repeat testing improve detection.(23)

4. The Addison's Clue: New darkening of scars acquired after disease onset is highly specific for Addison's disease and should prompt immediate investigation.(24)

5. The AN Risk Stratification: Severity of acanthosis nigricans correlates with cardiovascular risk independent of BMI; it serves as a visible marker of metabolic dysfunction requiring aggressive intervention.(25)

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Conclusion

The dermatologic manifestations of endocrine disease provide immediate, cost-free diagnostic information that precedes expensive laboratory testing. Pattern recognition of hair loss, systematic assessment of skin changes, and appreciation of high-stakes findings like acanthosis nigricans and hyperpigmentation transform the routine physical examination into a powerful diagnostic tool.

For the practicing internist, developing expertise in this derm-endocrine overlap enhances diagnostic accuracy, accelerates time to treatment, and addresses the significant psychological burden these visible changes impose on patients. In an era of algorithmic medicine, the skilled clinical examination retains irreplaceable value.

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