1. Endocrine Dysfunction in Cancer Survivors
1.1 Gonadal Dysfunction and Infertility
Cancer treatment can cause temporary or permanent gonadal dysfunction through direct gonadotoxic effects of alkylating chemotherapy, pelvic or gonadal radiation, surgical oophorectomy or orchiectomy, and endocrine therapies. The impact depends on the patient’s age at treatment, the specific agents used, cumulative doses, and baseline ovarian reserve or testicular function.
Gonadotoxicity Risk by Chemotherapy Agent
| Risk Level | Agents |
|---|
| High risk (>80% amenorrhea/azoospermia) | Cyclophosphamide (cumulative dose >5 g/m² in premenopausal women; >7.5 g/m² in men); busulfan; melphalan; procarbazine (especially in MOPP regimen); chlorambucil; conditioning regimens for stem cell transplant (TBI-based or high-dose alkylator) |
| Intermediate risk | Cisplatin (moderate cumulative doses); carboplatin; doxorubicin (at typical cumulative doses); lower-dose cyclophosphamide (e.g., AC ×4 in younger women); ifosfamide |
| Low risk (<20%) | Vincristine; bleomycin; methotrexate; 5-fluorouracil; targeted agents (trastuzumab, rituximab); immune checkpoint inhibitors (though immune-mediated hypophysitis can cause secondary hypogonadism) |
Radiation Effects on Gonadal Function
| Field | Effect |
|---|
| Pelvic or gonadal radiation | Dose-dependent ovarian failure (>6 Gy in adult women often causes permanent amenorrhea; lower doses may suffice in older women); testicular damage (spermatogenesis impaired at >1 Gy, often permanent at >6 Gy; Leydig cell dysfunction at >20 Gy) |
| Cranial radiation (hypothalamic-pituitary axis) | ≥30 Gy: high risk of gonadotropin deficiency (secondary hypogonadism); 18–30 Gy: intermediate risk; <18 Gy: precocious puberty in children more common than deficiency |
| Total body irradiation (TBI) | High risk of gonadal failure in both sexes |
Assessment of Gonadal Function in Survivors
| Sex | Assessment |
|---|
| Women | Menstrual history; symptoms of estrogen deficiency (vasomotor symptoms, vaginal dryness, libido changes); FSH, LH, estradiol (early follicular phase if menstruating); anti-Mullerian hormone (AMH) for assessment of ovarian reserve in women of reproductive age considering future fertility |
| Men | Symptoms of androgen deficiency (fatigue, decreased libido, erectile dysfunction, decreased muscle mass, depressed mood); morning testosterone (total and free); FSH, LH; semen analysis if fertility desired |
Fertility Preservation — Pre-Treatment Counseling and Options
All patients of reproductive age should receive fertility preservation counseling before initiating potentially gonadotoxic therapy. This is a time-sensitive discussion that should occur at diagnosis before treatment begins.
| Method | Sex | Details |
|---|
| Sperm cryopreservation | Male | Standard of care; should be offered to all postpubertal males; ideally multiple specimens; can be performed even in urgent situations before treatment |
| Oocyte or embryo cryopreservation | Female | Standard of care for postpubertal females; requires controlled ovarian stimulation (approximately 2 weeks); random-start protocols allow initiation at any point in menstrual cycle; letrozole-based stimulation protocols are preferred for estrogen-sensitive cancers |
| Ovarian tissue cryopreservation | Female | No longer considered experimental; option for prepubertal girls and women who cannot delay treatment for ovarian stimulation; tissue is reimplanted after treatment; live births reported |
| GnRH agonist (ovarian suppression) | Female | Co-administration of GnRH agonist (e.g., goserelin) during chemotherapy may preserve ovarian function, particularly in breast cancer patients; should be used as an adjunct to, not a substitute for, embryo/oocyte cryopreservation |
| Testicular tissue cryopreservation | Male (prepubertal) | Experimental; only option for prepubertal boys; performed at specialized centers |
| Testicular shielding | Male | During radiation therapy when gonads are near the radiation field |
| Ovarian transposition (oophoropexy) | Female | Surgical relocation of ovaries out of the radiation field before pelvic radiation; reduces but does not eliminate risk of ovarian failure due to scatter radiation |
1.2 Thyroid Dysfunction
Thyroid dysfunction is one of the most common endocrine late effects of cancer treatment, occurring in 20–50% of patients who receive radiation to the neck or upper mediastinum and in patients treated with certain systemic agents.
Causes of Thyroid Dysfunction in Cancer Survivors
| Cause | Typical Presentation | Agents/Modalities |
|---|
| Radiation-induced hypothyroidism | Primary hypothyroidism (elevated TSH, low free T4) | Neck or mediastinal radiation (risk increases with dose; most common at ≥30 Gy) |
| Immune checkpoint inhibitor thyroiditis | Thyrotoxicosis phase (weeks) followed by hypothyroidism | Nivolumab, pembrolizumab, ipilimumab, atezolizumab, durvalumab; incidence 5–15% |
| TKI-induced hypothyroidism | Primary hypothyroidism | Sunitinib (36–85%), sorafenib, axitinib, lenvatinib, cabozantinib |
| Radioactive iodine (thyroid cancer) | Hypothyroidism (expected; patients placed on levothyroxine) | I-131 therapy |
| Surgical (thyroidectomy) | Hypothyroidism, hypoparathyroidism | Total or partial thyroidectomy |
| Central hypothyroidism | Low free T4 with low/normal TSH | Cranial radiation ≥30 Gy to hypothalamic-pituitary axis; immune checkpoint inhibitor hypophysitis |
Thyroid Monitoring Protocol
| Patient Population | Test | Schedule |
|---|
| Post-neck/mediastinal radiation | TSH (±free T4) | Baseline, then every 6–12 months for the first 5 years, then annually lifelong |
| During/after immune checkpoint inhibitor therapy | TSH, free T4 | Before each cycle during treatment; every 6–12 months for 1–2 years after completion; sooner if symptomatic |
| During/after TKI therapy | TSH, free T4 | Every 4–6 weeks during treatment; resume normal screening after discontinuation |
| Post-cranial radiation (≥30 Gy to HP axis) | Free T4 (TSH may be unreliable) | Every 6–12 months; note: TSH may be normal or low in central hypothyroidism |
Cancer survivors are at increased risk for metabolic syndrome (central obesity, dyslipidemia, hypertension, insulin resistance/diabetes) due to multiple factors including androgen deprivation therapy, corticosteroid use, physical inactivity, weight gain during treatment, and direct treatment effects.
| Treatment | Metabolic Effect |
|---|
| Androgen deprivation therapy (ADT) | Increased visceral adiposity, insulin resistance, dyslipidemia, increased cardiovascular risk; metabolic syndrome in 50–75% of men on long-term ADT |
| Corticosteroids (prolonged use) | Hyperglycemia, weight gain, central adiposity, osteoporosis |
| Cranial radiation (hypothalamic-pituitary damage) | Growth hormone deficiency, central hypothyroidism, central adrenal insufficiency — all contribute to metabolic syndrome |
| Aromatase inhibitors | Dyslipidemia (cholesterol elevation), arthralgias, bone loss |
| Immune checkpoint inhibitors | Autoimmune diabetes (rare, ~0.2–1%, but can be fulminant type 1 DM) |
| Total body irradiation | Growth hormone deficiency, hypothyroidism, insulin resistance |
| Test | Frequency |
|---|
| Fasting glucose or HbA1c | Annually (more frequently during ADT, corticosteroid use, or ICI therapy) |
| Lipid panel | Annually (more frequently during ADT or aromatase inhibitor therapy) |
| Blood pressure | At every visit |
| Waist circumference and BMI | At every visit |
| Evaluation for metabolic syndrome (3 of 5 criteria: waist circumference, triglycerides, HDL, blood pressure, fasting glucose) | Annually |
2. Bone Health
2.1 Osteoporosis and Fracture Risk in Cancer Survivors
Multiple cancer treatments accelerate bone loss and increase fracture risk. The most significant exposures include aromatase inhibitors, androgen deprivation therapy, corticosteroids, and premature menopause from any cause.
Treatment Exposures Causing Bone Loss
| Exposure | Mechanism | Magnitude of Bone Loss |
|---|
| Aromatase inhibitors (anastrozole, letrozole, exemestane) | Profound estrogen suppression in postmenopausal women | BMD loss of 2–3% per year at spine and hip during treatment; fracture risk increased ~30–40% |
| ADT (GnRH agonists/antagonists, orchiectomy) | Testosterone and estrogen depletion | BMD loss of 2–4% per year at spine; fracture risk increases with duration of ADT |
| Premature menopause (chemotherapy-induced ovarian failure) | Loss of estrogen | Accelerated bone loss, particularly in younger women |
| Glucocorticoids (e.g., dexamethasone in myeloma, lymphoma regimens) | Inhibit osteoblast function, enhance osteoclast activity | Rapid bone loss within first 6 months; dose-dependent |
| Methotrexate (high-dose, prolonged) | Direct osteoblast toxicity | Particularly relevant in pediatric ALL survivors |
| Cranial radiation (GH deficiency) | Growth hormone deficiency → reduced bone formation | Relevant in childhood cancer survivors |
Bone Health Monitoring and Management
| Assessment | Recommendation |
|---|
| DXA scan (lumbar spine and hip) | Baseline before starting aromatase inhibitor or ADT; repeat every 1–2 years during treatment; consider baseline DXA in any survivor with ≥2 risk factors for osteoporosis |
| FRAX score | Calculate at baseline and periodically to guide treatment decisions (note: FRAX may underestimate fracture risk in cancer survivors on bone-toxic therapy) |
| Vitamin D level (25-OH vitamin D) | Check at baseline; supplement to maintain level ≥30 ng/mL |
| Calcium intake | Ensure total daily intake of 1,000–1,200 mg (diet + supplements) |
| Weight-bearing exercise | Recommend as tolerated for all survivors |
| Fall risk assessment | Particularly important for survivors with neuropathy, sarcopenia, or balance impairment |
Pharmacologic Bone Protection
| Agent | Indication | Dosing |
|---|
| Bisphosphonates (zoledronic acid, alendronate, risedronate) | T-score ≤ -2.0 or T-score ≤ -1.5 with additional risk factors; or ≥ -1.0 with high-risk therapy (ADT, AI) and other risk factors per FRAX | Zoledronic acid 4 mg IV every 6 months; or alendronate 70 mg PO weekly; or risedronate 35 mg PO weekly |
| Denosumab | Alternative to bisphosphonates; T-score ≤ -2.0 or high-risk patients; particularly useful in renal impairment (where bisphosphonates are contraindicated) | 60 mg SC every 6 months |
| Vitamin D supplementation | All patients on aromatase inhibitors or ADT | Cholecalciferol 1,000–2,000 IU daily (higher doses if deficient) |
Important note on denosumab: Discontinuation of denosumab is associated with rapid rebound bone loss and increased vertebral fracture risk. If denosumab is stopped, transition to a bisphosphonate to mitigate rebound.
3. Cognitive Dysfunction (“Chemobrain”)
3.1 Definition and Epidemiology
Cancer-related cognitive impairment (CRCI) refers to objectively measurable or subjectively reported deficits in cognitive domains — including attention, concentration, processing speed, executive function, and memory — that develop during or after cancer treatment. Approximately 30–75% of cancer survivors report cognitive symptoms during or after treatment, and 20–35% experience persistent cognitive difficulties months to years after treatment completion.
3.2 Contributing Factors
| Factor | Details |
|---|
| Chemotherapy (“chemobrain”) | Alkylating agents, antimetabolites (methotrexate, 5-FU), platinum agents; mechanisms include oxidative stress, neuroinflammation, white matter damage, and hippocampal neurogenesis disruption |
| Endocrine therapy | Tamoxifen and aromatase inhibitors are associated with subjective cognitive complaints; estrogen deprivation may contribute |
| Cranial radiation | Dose-dependent; particularly relevant in pediatric brain tumor survivors and adults with primary CNS tumors or prophylactic cranial irradiation |
| Intrathecal chemotherapy | Methotrexate, cytarabine — white matter changes, particularly in combination with cranial radiation |
| Immunotherapy | Autoimmune encephalitis (rare); fatigue-related cognitive effects |
| Non-treatment factors | Cancer-related fatigue, depression, anxiety, sleep disturbance, pain, anemia, thyroid dysfunction, medications (opioids, benzodiazepines, anticholinergics) |
3.3 Assessment
| Method | Details |
|---|
| Screening tools | Patient-reported measures: FACT-Cog (Functional Assessment of Cancer Therapy – Cognitive Function); PROMIS Cognitive Function Short Form |
| Neuropsychological testing | Formal testing by a neuropsychologist is the gold standard; assesses attention, processing speed, executive function, verbal and visual memory, language; recommended when cognitive complaints are persistent, functionally impairing, or disproportionate to clinical expectations |
| Evaluate reversible contributors | TSH, B12, hemoglobin, depression screening (PHQ-9), sleep assessment, medication review (anticholinergics, benzodiazepines, opioids) |
3.4 Management
| Intervention | Evidence and Recommendation |
|---|
| Cognitive rehabilitation | Structured cognitive rehabilitation programs (compensatory strategies, attention training, memory strategies) have shown benefit in randomized trials; referral to neuropsychology or occupational therapy |
| Physical exercise | Moderate aerobic exercise (150 minutes/week) is associated with improved cognitive function in cancer survivors; one of the most evidence-supported interventions |
| Address modifiable factors | Treat depression, optimize sleep, manage pain, correct anemia and thyroid dysfunction, discontinue or reduce cognitive-impairing medications |
| Mindfulness-based stress reduction (MBSR) | Emerging evidence for improvement in self-reported cognitive function and associated distress |
| Pharmacotherapy | Limited evidence; psychostimulants (methylphenidate, modafinil) have been studied with mixed results and are not routinely recommended but may be considered in refractory cases; donepezil has shown some benefit in cranial radiation–related cognitive decline |
4.1 Definition and Prevalence
Cancer-related fatigue (CRF) is a distressing, persistent, subjective sense of physical, emotional, or cognitive tiredness related to cancer or its treatment that is not proportional to recent activity and interferes with usual functioning. It is the most common symptom reported by cancer survivors, affecting 25–60% of patients months to years after treatment completion.
4.2 Evaluation
A systematic evaluation should be performed for all survivors reporting fatigue:
| Step | Assessment |
|---|
| Quantify fatigue severity | Numeric rating scale (0–10); Brief Fatigue Inventory (BFI); FACIT-Fatigue scale |
| Screen for treatable causes | CBC (anemia), TSH, CMP (renal/hepatic dysfunction, electrolytes), cortisol (if adrenal insufficiency suspected), vitamin D, B12, glucose/HbA1c |
| Assess contributing factors | Depression and anxiety (PHQ-9, GAD-7); sleep disorders (insomnia, obstructive sleep apnea); pain; deconditioning; nutritional deficits; medications (sedatives, beta-blockers, opioids); cardiac dysfunction |
| Assess functional impact | Activities of daily living; work capacity; social functioning |
4.3 Management
| Intervention | Level of Evidence | Details |
|---|
| Physical activity | Strong | Most effective intervention for CRF; aerobic exercise (150 min/week moderate or 75 min/week vigorous) + resistance training (2–3 sessions/week); supervised exercise programs preferred; individualized to functional status |
| Cognitive-behavioral therapy (CBT) | Strong | CBT for fatigue addresses maladaptive activity patterns, sleep hygiene, and cognitive restructuring; reduces fatigue severity |
| Treatment of underlying contributors | Strong | Correct anemia (EPO if Hb <10 and on chemotherapy; transfusion; iron supplementation); treat hypothyroidism; treat depression; optimize sleep; treat pain; address cardiac dysfunction |
| Sleep optimization | Moderate | CBT for insomnia (CBT-I); sleep hygiene education; melatonin (1–3 mg) if sleep initiation difficulty; avoid chronic use of sedative-hypnotics |
| Mind-body interventions | Moderate | Yoga, tai chi, mindfulness meditation — shown to reduce fatigue in multiple RCTs |
| Psychostimulants | Limited | Methylphenidate (5–10 mg in the morning, with optional 5 mg at noon) may be considered for severe fatigue unresponsive to other interventions; modafinil 100–200 mg daily as alternative; use should be time-limited and re-evaluated |
5. Chemotherapy-Induced Peripheral Neuropathy (CIPN)
5.1 Overview
CIPN is a common and potentially disabling late effect caused by neurotoxic chemotherapy agents. It typically presents as a length-dependent, symmetric, sensory-predominant neuropathy affecting the distal extremities (glove-and-stocking distribution). Chronic CIPN persists in 30–40% of patients beyond 6 months after treatment completion and may be permanent in some cases.
5.2 High-Risk Agents
| Agent | CIPN Characteristics | Incidence of Persistent CIPN |
|---|
| Taxanes (paclitaxel, docetaxel) | Sensory > motor; numbness, tingling, pain in hands and feet; paclitaxel more neurotoxic than docetaxel per cycle | 20–40% at 1–2 years post-treatment |
| Platinum agents (cisplatin, oxaliplatin, carboplatin) | Cisplatin: cumulative dose-dependent sensory neuropathy; oxaliplatin: acute cold-triggered dysesthesias + chronic sensory neuropathy; “coasting” (worsening after treatment cessation) common | Cisplatin: 20–30% at 2 years; Oxaliplatin: 10–30% chronic |
| Vinca alkaloids (vincristine) | Sensory and motor; autonomic neuropathy (constipation); highest risk in children | 10–20% persistent in children |
| Bortezomib | Painful sensory neuropathy; may be reversible with dose modification | 10–20% persistent |
| Thalidomide / lenalidomide | Cumulative, dose-dependent sensory neuropathy | Thalidomide: 20–40%; lenalidomide: lower risk |
5.3 Assessment
| Method | Details |
|---|
| NCI CTCAE grading | Grade 1: asymptomatic or mild; Grade 2: moderate, limiting ADLs; Grade 3: severe, limiting self-care ADLs; Grade 4: life-threatening |
| Validated tools | EORTC QLQ-CIPN20; FACT/GOG-Ntx; Total Neuropathy Score (TNS-c) |
| Nerve conduction studies / EMG | Not required for diagnosis but recommended when diagnosis is uncertain, presentation is atypical (asymmetric, motor-predominant, rapidly progressive), or alternative diagnoses need to be excluded (B12 deficiency, diabetic neuropathy, autoimmune neuropathy) |
| Evaluate for concurrent neuropathic causes | B12, folate, HbA1c/fasting glucose, TSH, serum protein electrophoresis (if paraprotein neuropathy suspected); HIV testing if risk factors |
5.4 Management
| Intervention | Recommendation |
|---|
| Duloxetine | Best evidence for treatment of painful CIPN; 30 mg daily for 1 week, then 60 mg daily; demonstrated benefit in a large randomized trial for oxaliplatin- and taxane-induced painful CIPN |
| Gabapentin / pregabalin | Commonly used despite limited evidence specific to CIPN; gabapentin 300 mg TID titrated to 3,600 mg/day; pregabalin 75 mg BID titrated to 300 mg/day; may be more effective for painful neuropathy |
| Tricyclic antidepressants | Nortriptyline or amitriptyline 10–25 mg at bedtime, titrated to 75–100 mg; extrapolated from non-cancer neuropathic pain evidence; use with caution in elderly (anticholinergic effects) |
| Topical agents | Capsaicin 8% patch; menthol-based creams; lidocaine 5% patches — provide local relief for localized painful areas |
| Physical and occupational therapy | Balance training, strengthening exercises, sensory retraining, compensatory strategies, assistive devices; reduces fall risk |
| Exercise | Regular physical activity, particularly balance-focused exercise, may improve CIPN symptoms and functional status |
| Acupuncture | Emerging evidence from randomized trials suggesting benefit for CIPN symptoms; reasonable to offer as adjunctive therapy |
| Prevention during treatment | No pharmacologic agent has been conclusively proven to prevent CIPN; avoid ice (cryotherapy) for oxaliplatin-related acute neuropathy; dose modification (reduction or discontinuation) remains the most effective prevention strategy |
6. Lymphedema
6.1 Overview
Lymphedema is a chronic condition resulting from impaired lymphatic drainage, causing swelling, tissue fibrosis, and functional impairment. In cancer survivors, it most commonly follows axillary lymph node dissection (breast cancer) or inguinal/pelvic lymphadenectomy (gynecologic, urologic, and melanoma cancers), particularly when combined with regional radiation therapy. Incidence ranges from 5–50% depending on the extent of surgery, radiation, and patient risk factors.
6.2 Risk Factors
| Risk Factor | Details |
|---|
| Extent of lymph node surgery | Axillary lymph node dissection (ALND) » sentinel lymph node biopsy alone; radical inguinal lymphadenectomy |
| Regional radiation therapy | Axillary, supraclavicular, inguinal, or pelvic radiation significantly increases risk, particularly combined with lymphadenectomy |
| Obesity (BMI ≥30) | One of the strongest modifiable risk factors |
| Taxane chemotherapy | Independent risk factor for upper extremity lymphedema after breast cancer surgery |
| Infection (cellulitis) in the at-risk limb | Can trigger or worsen lymphedema |
| Number of lymph nodes removed | Higher node count correlates with higher risk |
6.3 Prevention
| Strategy | Details |
|---|
| Sentinel lymph node biopsy (when oncologically appropriate) | Substantially reduces lymphedema risk compared to complete lymph node dissection |
| Prospective surveillance model | Baseline and serial arm/limb circumference or bioimpedance measurements at regular intervals post-operatively; allows detection of subclinical lymphedema and early intervention |
| Patient education | Skin care, avoidance of blood pressure cuffs and venipuncture on the affected side (controversial but commonly recommended), prompt treatment of skin infections, weight management, gradual progressive exercise |
| Weight management | Maintain or achieve healthy BMI |
| Axillary reverse mapping | Surgical technique to identify and preserve arm-draining lymphatics during axillary dissection; being studied in clinical trials |
6.4 Staging and Assessment
| Stage | Description |
|---|
| Stage 0 (subclinical) | Impaired lymphatic drainage detectable by bioimpedance or lymphoscintigraphy, but no visible swelling; may persist for months to years before progressing |
| Stage I (reversible) | Soft, pitting edema that reduces with limb elevation; no tissue fibrosis |
| Stage II (spontaneously irreversible) | Non-pitting edema; tissue fibrosis present; does not resolve with elevation alone |
| Stage III (lymphostatic elephantiasis) | Severe fibrosis, skin changes (papillomatosis, hyperkeratosis), massive limb swelling; rare with appropriate management |
Measurement Methods
| Method | Details |
|---|
| Circumferential measurement | Tape measurement at defined points; ≥2 cm difference from the contralateral limb or ≥10% volume difference is commonly used as a diagnostic threshold |
| Bioimpedance spectroscopy (L-Dex) | Measures extracellular fluid; useful for subclinical detection; L-Dex change of ≥10 units from baseline suggests subclinical lymphedema |
| Volume displacement (water volumetry) | Gold standard for volume measurement; less practical in clinical settings |
| Perometry | Infrared optoelectronic limb measurement; accurate and reproducible |
6.5 Management
| Intervention | Details |
|---|
| Complete decongestive therapy (CDT) | Gold standard treatment; consists of Phase 1 (intensive reduction): manual lymphatic drainage (MLD), short-stretch compression bandaging, decongestive exercises, skin care (typically 2–4 weeks, daily sessions); Phase 2 (maintenance): compression garments, self-MLD, exercise, skin care |
| Compression garments | Fitted compression sleeves/stockings (20–30 mmHg or 30–40 mmHg); worn during waking hours; must be properly fitted and replaced every 4–6 months |
| Exercise | Progressive, supervised resistance and aerobic exercise is safe and does not worsen lymphedema; may improve lymphedema outcomes; compression garment should be worn during exercise |
| Pneumatic compression devices | Intermittent pneumatic compression as adjunct to CDT; home-based devices available for maintenance therapy |
| Surgical options | Lymphovenous anastomosis (microsurgical); vascularized lymph node transfer; liposuction (for late-stage fibrotic lymphedema unresponsive to conservative management); considered in refractory cases |
| Skin care and infection prevention | Meticulous skin hygiene; emollients; prompt treatment of cellulitis with antibiotics (typically beta-lactam covering streptococci and staphylococci); prophylactic antibiotics (penicillin V 250 mg BID) for recurrent cellulitis (≥2 episodes per year) |
| Weight management | Weight loss in overweight/obese patients can significantly reduce limb volume |
7. Endocrine Late Effects Screening Summary
| Late Effect | At-Risk Population | Screening Test | Schedule |
|---|
| Premature ovarian insufficiency | Women who received alkylating agents, pelvic/gonadal radiation, TBI | FSH, estradiol; menstrual history; symptoms assessment | At treatment completion; then as indicated by symptoms |
| Male hypogonadism | Men who received alkylating agents, testicular radiation, TBI | AM testosterone, FSH, LH | At treatment completion; then annually if symptomatic or if on ADT |
| Hypothyroidism (primary) | Neck/mediastinal radiation; TKI therapy; ICI therapy | TSH, free T4 | Every 6–12 months starting 1 year post-exposure; annually lifelong post-radiation |
| Hypothyroidism (central) | Cranial radiation ≥30 Gy | Free T4 (TSH unreliable) | Every 6–12 months lifelong |
| Growth hormone deficiency | Cranial radiation (particularly childhood); TBI | IGF-1; GH stimulation testing if clinical suspicion | Annually in childhood survivors; consider testing in adults with fatigue, reduced QOL, abnormal body composition |
| Adrenal insufficiency | Cranial radiation ≥30 Gy; ICI therapy (hypophysitis); prolonged corticosteroid use | AM cortisol; ACTH stimulation test if suggestive | Annually after cranial radiation; during and after ICI therapy if symptomatic |
| Diabetes/metabolic syndrome | ADT; corticosteroids; TBI; cranial radiation; ICI therapy | Fasting glucose/HbA1c; lipid panel; BP; waist circumference | Annually |
| Osteoporosis | AI therapy; ADT; corticosteroids; premature menopause; methotrexate | DXA; FRAX | Baseline before AI/ADT; every 1–2 years during treatment |
References