Undifferentiated Fatigue — Viva Defence

Long case viva — multifactorial fatigue

Candidate's opening statement (SASPOP)

"Doctor, my patient is Mrs MA, a 62-year-old woman with type 2 diabetes, hypothyroidism and obesity who works part-time as an administrative officer and who presents with a 3-month history of worsening fatigue that now limits her work and her self-care. She has multiple contributors: the uncontrolled diabetes with an HbA1c of 74, the iron deficiency with a ferritin of 18, the under-treated hypothyroidism, the uncontrolled obstructive sleep apnoea, the deconditioning, the beta-blockade, and a positive PHQ-2 of 5 suggesting a likely comorbid depression. Her problems are: the multifactorial fatigue; the uncontrolled type 2 diabetes; the iron deficiency; the under-treated hypothyroidism; the obstructive sleep apnoea; the likely depression; and the polypharmacy." [1]

Problem list

1. Multifactorial fatigue — physiological, physical and psychological contributors.
2. Uncontrolled type 2 diabetes (HbA1c 74 mmol per mol) — osmotic fatigue and deconditioning.
3. Iron deficiency (ferritin 18 micrograms per litre) — with the investigation of the underlying cause pending.
4. Under-treated hypothyroidism — the TSH to be confirmed and the levothyroxine optimised.
5. Obstructive sleep apnoea (STOP-Bang 5) — uncontrolled, the CPAP adherence to be assessed.
6. Likely comorbid depression (PHQ-2 of 5) — the full assessment and the treatment pending.
7. Polypharmacy — the beta-blocker and the statin as the contributory drugs. [1]

Integrated management plan

The principle: treat each contributor, validate the symptom, and avoid the single-cause anchoring. The fatigue is multifactorial, and the integrated management is the addressing of each contributor in turn. [1]

Investigations — the targeted Tier 2. Confirm the TSH and the free T4. Confirm the HbA1c and the renal function. Perform the coeliac screen (the tissue transglutaminase IgA with the total IgA) given the iron deficiency. Review the iron studies and commence the oral iron. Assess the CPAP adherence and the data download, and consider the repeat polysomnogram if the adherence is poor. Perform the full mood assessment (the PHQ-9) given the positive PHQ-2. Consider the polysomnogram if the sleep apnoea is unconfirmed. [1]

The diabetes. Optimise the glycaemic control — the individualised HbA1c target (typically 53 to 64 mmol per mol in this older patient with the comorbidity), the review of the current regimen, the addition of the SGLT2 inhibitor (which also benefits the heart failure and the weight) or the GLP-1 receptor agonist (which benefits the weight), the lifestyle intervention, and the cardiovascular risk reduction. The osmotic fatigue will improve as the glycaemic control improves. [1]

The iron deficiency. Commence the oral ferrous sulfate (65 to 100 mg elemental iron daily or on alternate days, with the vitamin C), reassess the haemoglobin and the ferritin at 4 weeks, and investigate the underlying cause — the gastrointestinal work-up (the faecal immunochemical test, the gastroscopy and the colonoscopy) given the age and the iron deficiency, and the gynaecological review if applicable. [1]

The hypothyroidism. Confirm the TSH, optimise the levothyroxine (the dose adjustment, the 6-week reassessment), and counsel the patient on the empty-stomach dosing and the drug interactions (the calcium, the iron, the proton pump inhibitor). [1]

The sleep apnoea. Assess the CPAP adherence and the symptom control; if the adherence is poor, the mask refit, the pressure adjustment, and the behavioural support. The weight loss and the exercise. The avoidance of the alcohol and the sedatives. [1]

The depression. The full PHQ-9 and the suicide risk assessment. The evidence-based treatment — the CBT and the SSRI (the sertraline as the first-line, with the 4 to 6 week onset), the addressing of the psychosocial stressors. [1]

The medication review. Consider the beta-blocker dose reduction or the switch (if the indication allows), and the statin holiday if the muscle symptoms are prominent (with the rechallenge at the lower dose or the different statin). [1]

The communication and the shared decision-making. Explain the multifactorial nature of the fatigue, the prioritisation of the management (the diabetes, the iron, the thyroid, the sleep, the mood, the medication), the realistic timeline (the improvement over weeks to months), the red flags to report, and the planned review. [1]

Examiner probing questions

Examiner: "Why is the PHQ-2 score of 5 not a diagnosis of depression?" The PHQ-2 is a screening tool, not a diagnostic instrument. A score of 3 or more has a sensitivity of 83 per cent and a specificity of 92 per cent for the major depressive disorder, per Kroenke. The positive screen is the prompt to the full diagnostic assessment — the DSM-5 criteria, the duration, the severity, the functional impairment, the bipolar exclusion, and the suicide risk assessment. The registrar who prescribes the antidepressant on the basis of the PHQ-2 alone has not performed the proper assessment. [1]

Examiner: "How do you explain the fatigue to this patient without dismissing her?" I validate the fatigue as a real and disabling symptom with multiple identifiable contributors. I explain that the diabetes, the iron deficiency, the thyroid, the sleep apnoea and the mood each contribute, and that the addressing of each in turn will improve the fatigue over weeks to months. I set the realistic expectation, I offer the clear plan, and I arrange the planned review. The patient who feels heard and who has a plan is far less likely to re-present or to seek the alternative-medicine pathway. [1]

Examiner: "What is the single most important safety assessment at this visit?" The suicide risk assessment — given the positive PHQ-2 and the depression. The registrar asks directly about the suicidal ideation, the intent, the plan and the means, and acts on the finding. The safety assessment is mandatory at every visit with the suspected depression. [1]

Branching scenario — ME/CFS

Examiner: "Now consider a 30-year-old woman who presents with 14 months of severe fatigue, unrefreshing sleep, and a marked worsening of all symptoms 24 to 48 hours after any exertion, taking four to five days to recover. Her Tier 1 screen is normal. What is the diagnosis, and what is the management?"

This is the myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS). The four core criteria are met: the disabling fatigue of more than 6 months, the post-exertional malaise (the delayed worsening with the slow recovery), the unrefreshing sleep, and the cognitive impairment. The 2015 IOM report established the diagnostic criteria; the 2021 NICE NG206 guideline is the management reference. [1]

Examiner: "What is the key management principle, and what treatment has been withdrawn?" The key principle is the energy management and the pacing — staying within the energy envelope, avoiding the activities that trigger the post-exertional malaise. The 2021 NICE NG206 guideline withdrew the graded exercise therapy (GET) for the ME/CFS because of the risk of harm from the PEM. The CBT is offered as a supportive treatment (to help the patient cope), NOT as a curative treatment. The registrar who prescribes the graded exercise to a ME/CFS patient has misread the guideline and may worsen the patient. [1]

Examiner: "Why was the GET withdrawn?" The NICE committee reviewed the evidence and found that the GET — the programme of the fixed incremental increases in the physical activity — could cause the harm by forcing the patients to exceed the energy limits and triggering the PEM. The earlier evidence (the PACE trial, the 2007 NICE CG53) has been heavily criticised for the outcome switching, the loose criteria, the lack of the objective measures, and the failure to report the harm. The patient-reported harm and the re-evaluation of the evidence drove the revision. [1]

Branching scenario — Addison disease

Examiner: "And what if the 62-year-old woman instead presented with a 6 kg weight loss, a postural blood pressure drop, hyperpigmentation of the palmar creases and the buccal mucosa, a sodium of 128 and a potassium of 5.4?"

That is the primary adrenal insufficiency (Addison disease) until proven otherwise. The fatigue, the weight loss, the salt craving, the postural hypotension, the hyperpigmentation (from the elevated pro-opiomelanocortin), the hyponatraemia with the hyperkalaemia, and the hypoglycaemia are the classic presentation. [1]

Examiner: "What test confirms the diagnosis?" The 250 microgram short Synacthen (tetracosactide) test, per the 2016 Endocrine Society guideline. The cortisol at 0, 30 and 60 minutes after the intravenous or the intramuscular tetracosactide; the peak cortisol below 500 nmol per litre confirms the adrenal insufficiency. The ACTH is markedly elevated in the primary disease; the 21-hydroxylase antibodies confirm the autoimmune aetiology. [1]

Examiner: "What is the management, and what is the critical patient-education point?" The hydrocortisone (15 to 25 mg daily in two or three divided doses) and the fludrocortisone (50 to 200 micrograms daily). The critical patient-education point is the sick-day rules — the doubling or the trebling of the hydrocortisone during the illness, the emergency intramuscular hydrocortisone (the 100 mg), the medical alert bracelet, and the adrenal crisis action plan. The missed sick-day rule is the missed adrenal crisis. [1]

Short-case discussion — the bedside discriminators

Examiner: "Examine this fatigued patient. Focus on the bedside signs that discriminate the systemic causes."

My routine: the general inspection (the cachexia, the obesity, the pallor, the pigmentation); the vital signs including the lying and the standing blood pressure; the hands (the pallor of the palmar creases, the koilonychia of the iron deficiency, the clubbing of the systemic disease); the thyroid (the goitre, the bruit, the eye signs); the cardiovascular (the JVP, the apex, the gallop, the murmurs); the respiratory (the crackles, the wheeze); the abdominal (the hepatosplenomegaly, the masses); the lymph nodes (the cervical, the supraclavicular, the axillary, the epitrochlear, the inguinal); and the skin (the hyperpigmentation of the Addison disease, the pallor, the bruising). [1]

Presentation: "The patient is pale on inspection. There is pallor of the palmar creases. The nails show koilonychia — the spoon-shaped, thin, brittle nails consistent with the iron deficiency. The lying blood pressure is 110/70 and the standing blood pressure at 1 minute is 92/60, a postural drop consistent with the mineralocorticoid deficiency or the dehydration. There is increased pigmentation of the palmar creases and the buccal mucosa, consistent with the elevated pro-opiomelanocortin of the primary adrenal insufficiency. There is no goitre and no eye signs. The cardiovascular, the respiratory and the abdominal examinations are unremarkable. There is no lymphadenopathy. The findings are consistent with the iron deficiency and the primary adrenal insufficiency, and I would confirm with the iron studies and the short Synacthen test." [1]

Examiner: "What is the single most important bedside sign you looked for?" The hyperpigmentation of the palmar creases and the buccal mucosa — the sign that distinguishes the Addison disease from the depression or the chronic stress. The registrar who examines the fatigued patient and does not turn the hands over and look at the palmar creases has missed the diagnosis at the bedside. [1]