What could be causing my fatigue, easy bruising, and central weight gain?

Evaluation of Fatigue, Easy Bruising, and Central Weight Gain

The combination of fatigue, easy bruising, and central weight gain strongly suggests Cushing's syndrome (hypercortisolism) and requires immediate endocrine evaluation with an overnight 1-mg dexamethasone suppression test or 24-hour urinary free cortisol. 1

Primary Differential Diagnosis

This triad of symptoms points to several critical diagnoses that must be systematically excluded:

Cushing's Syndrome (Most Likely)

• Central obesity with weight gain, fatigue, and easy bruising are classic presenting features 1
• Physical examination findings to assess include: moon facies, dorsal and supraclavicular fat pads, wide (≥1 cm) violaceous striae, proximal muscle weakness, and hirsutism 1
• Initial screening should be overnight 1-mg dexamethasone suppression test, followed by 24-hour urinary free cortisol (preferably multiple collections) and midnight salivary cortisol if initial test is abnormal 1
• Additional symptoms may include rapid weight gain with central distribution, proximal muscle weakness, depression, and hyperglycemia 1

Hematologic Disorders

• Easy bruising with fatigue warrants complete blood count, platelet count, platelet function studies, and von Willebrand screen 1
• Immune checkpoint inhibitor-induced thrombocytopenia presents with easy or excessive bruising, petechiae (usually on lower legs), and bleeding from gums or nose 1
• Acute lymphoblastic leukemia presents with fatigue, easy bruising or bleeding, and constitutional symptoms including weight changes 1
• If easy bruising is present, obtain history regarding bleeding problems before proceeding with CBC, platelet count, platelet function study, and von Willebrand screen 1

Thyroid Dysfunction

• Hypothyroidism is one of the first and most important causes to investigate, as it frequently presents with fatigue and nonspecific symptoms 2
• Hypothyroid patients may present with weight gain, dry skin, cold intolerance, constipation, and hoarseness 1
• Screen with thyroid-stimulating hormone and free thyroxine 1, 2

Systematic Diagnostic Approach

Initial Laboratory Evaluation

• Screen fatigue severity immediately using a 0-10 numeric rating scale, where scores of 4-10 indicate moderate-to-severe fatigue requiring comprehensive evaluation 3
• Core laboratory testing includes: 2, 3
  • Complete blood count with differential
  • Comprehensive metabolic panel
  • Thyroid-stimulating hormone
  • Cortisol assessment (overnight dexamethasone suppression test or 24-hour urinary free cortisol)
  • Platelet count and coagulation studies

Targeted History Elements

• Assess fatigue onset, pattern, duration, changes over time, and interference with daily activities 3, 4
• Evaluate for associated symptoms including pain, dyspnea, fever, and changes in bowel/bladder habits 3
• Obtain detailed history regarding easy bruising or bleeding problems, including spontaneous bruising, bleeding from gums or nose, and blood in urine or stool 1
• Document weight gain pattern, particularly whether it is rapid and centrally distributed 1

Physical Examination Priorities

• Examine for Cushing's stigmata: central obesity, moon facies, dorsal/supraclavicular fat pads, wide violaceous striae, proximal muscle weakness 1
• Assess for petechiae, particularly on lower extremities, and signs of subcutaneous bleeding 1
• Evaluate for lymphadenopathy, hepatosplenomegaly, and signs of thyroid dysfunction 1

Critical Pitfalls to Avoid

• Laboratory results affect management in only about 5% of fatigue cases, but core testing remains essential to rule out treatable causes 2
• Do not overlook psychological causes such as depression (affecting 18.5% of patients with fatigue) and anxiety, as these require specific assessment 2, 5
• Never assume fatigue is solely due to one cause, as multiple contributing factors often coexist 4
• Missing medication side effects can perpetuate fatigue—systematically review all prescription and over-the-counter medications 2
• Sleep disorders affect 30-75% of patients with fatigue and must be specifically evaluated 2

Management Strategy

Address Reversible Causes First

• Correct anemia, treat depression and anxiety disorders, manage pain adequately, optimize sleep hygiene, and adjust or discontinue offending medications before considering additional interventions 3
• Assess for nutritional deficiencies including vitamin B6, B12, folate, ferritin, zinc, vitamin D, magnesium, copper, phosphate, and calcium 2

Specialist Referral Indications

• Refer to endocrinology if Cushing's syndrome is suspected based on clinical presentation and screening tests 1
• Refer to hematology for abnormal CBC, thrombocytopenia, or positive coagulation studies 1
• Consider oncology referral if constitutional symptoms, lymphadenopathy, or hepatosplenomegaly are present 1

Follow-Up Protocol

• Rescreen fatigue severity at each visit and monitor weight trends closely 3
• Reassess after treating identified contributing factors 3, 4
• Pursue additional investigation if symptoms persist or worsen despite treatment, new symptoms develop, or weight loss/gain continues 3