Pathophysiology
P-I-10. Endocrine disorder, Case 2
内分泌疾患 症例2
A 38-year-old female patient presents at her GP with the following symptoms: muscle weakness, fatigue. She has lost 10 kg within the last 6 months; she is not on a diet. She often has nausea. She often gets dizzy before meals; the dizziness increases if she stands up from a lying or sitting position.
Blood pressure: 96/68 mmHg, pulse 88/min, respiratory rate: 14/min, body temperature 36.5 °C. After standing up her systolic blood pressure dropped by 20 mmHg. Height: 160 cm, weight: 50 kg, BMI: 19.5.
Physical examination: Thin female patient in moderate nutritional condition. Significantly dark pigmentation of skin (does not visit solariums, does not like sunbathing because she feels worse in the heat). Lungs: no abnormalities; heart: normal rhythmic heart sounds, occasionally an extrasystole can be heard, soft pulse. Abdomen below the level of chest, liver, spleen not palpable. No severe neurological abnormalities. Muscle weakness when pressing hands.
Patient does not take medication regularly, except from August to October when she continuously takes antihistamines for ragweed allergy. No known drug intolerance.
Family history: Her mother has had type I diabetes since the age of 4; her 34-year-old sister was diagnosed with Hashimoto-thyroiditis 2 years ago. Occupational history: negative.
Other abnormalities upon examination: ECG: sinus rhythm, heart rate: 92/min, axis: 70°. The ECG shows 2 ventricular extrasystoles; the T waves are prominently high in all 12 leads. QT distance: 0.32 s. Signs of hyperkalemia? The following laboratory findings should be highlighted: serum sodium: 125 mmol/l. Serum potassium: 6.8 mmol/l. Blood sugar (fasting): 3.0 mmol/l.
Key Quotes & What They Tell Us
| Quote / Value | Interpretation |
|---|---|
| “muscle weakness, fatigue”; “lost 10 kg … not on a diet”; “often has nausea” | Cortisol deficiency → weakness, weight loss, and GI symptoms |
| BP 96/68 mmHg; systolic drop of 20 mmHg on standing; dizziness before meals | Orthostatic hypotension from aldosterone/cortisol deficiency; pre-meal dizziness reflects hypoglycaemia |
| “Significantly dark pigmentation of skin” (no sun exposure) | Elevated ACTH/MSH from loss of cortisol feedback → hyperpigmentation (hallmark of primary adrenal failure) |
| Na⁺ 125 mmol/L (low); K⁺ 6.8 mmol/L (high) | Aldosterone deficiency → salt-wasting hyponatraemia and hyperkalaemia |
| Fasting glucose 3.0 mmol/L (low) | Cortisol deficiency impairs gluconeogenesis → hypoglycaemia |
| ECG: “T waves … prominently high in all 12 leads” | Peaked T waves — electrocardiographic sign of hyperkalaemia |
| Mother type 1 diabetes; sister Hashimoto thyroiditis | Family autoimmunity → supports autoimmune adrenalitis / polyglandular syndrome |
Key Points
- Diagnosis: Primary adrenal insufficiency (Addison’s disease), likely autoimmune (autoimmune polyglandular syndrome given family history).
- Pathophysiology: Destruction of the adrenal cortex → deficiency of both cortisol and aldosterone.
- Cortisol loss: Fatigue, weight loss, nausea, hypoglycaemia.
- Aldosterone loss: Hyponatraemia, hyperkalaemia, and orthostatic hypotension (salt-wasting).
- Distinguishing sign: Skin hyperpigmentation from high ACTH — specific to primary (not secondary) adrenal failure.
- Danger: Risk of life-threatening adrenal (Addisonian) crisis; hyperkalaemia threatens cardiac arrhythmia.
一問一答
▶What is the underlying pathophysiology of Addison's disease in this case?
Destruction of the adrenal cortex causing deficiency of both cortisol and aldosterone.
▶In the Case 2 patient (weight loss, hyperpigmentation, low Na⁺, high K⁺), what is the diagnosis?
Primary adrenal insufficiency (Addison's disease), likely autoimmune (autoimmune polyglandular syndrome given the family history).
▶Which findings in Case 2 reflect aldosterone deficiency?
Hyponatremia (Na⁺ 125), hyperkalemia (K⁺ 6.8), and orthostatic hypotension (salt-wasting).
▶Which symptoms in Case 2 reflect cortisol deficiency?
Muscle weakness, fatigue, unintentional weight loss, nausea, and hypoglycemia.
▶Why does skin hyperpigmentation occur in primary adrenal insufficiency?
Loss of cortisol feedback raises ACTH/MSH, causing hyperpigmentation — a hallmark specific to primary (not secondary) adrenal failure.
▶Why does the patient in Case 2 have hypoglycemia (fasting glucose 3.0 mmol/L)?
Cortisol deficiency impairs gluconeogenesis.
▶What ECG finding in Case 2 indicates hyperkalemia?
Prominently high (peaked) T waves in all 12 leads.
▶How does the family history support the diagnosis in Case 2?
Mother's type 1 diabetes and sister's Hashimoto thyroiditis indicate familial autoimmunity, supporting autoimmune adrenalitis/polyglandular syndrome.
▶What does the orthostatic drop in systolic BP of 20 mmHg indicate in Case 2?
Orthostatic hypotension from aldosterone/cortisol deficiency.
▶Why does the patient get dizzy before meals?
Pre-meal hypoglycemia (from cortisol deficiency impairing glucose maintenance).
▶What is the major life-threatening danger in Case 2?
Risk of an Addisonian (adrenal) crisis, and hyperkalemia threatening cardiac arrhythmia.
▶How does hyperpigmentation help distinguish primary from secondary adrenal insufficiency?
Primary failure has high ACTH causing hyperpigmentation; secondary (pituitary) failure has low ACTH and no hyperpigmentation.
▶Why does the patient feel worse in the heat?
Impaired stress response and salt/volume depletion reduce tolerance to heat stress.
▶What is autoimmune polyglandular syndrome?
A condition where autoimmune destruction affects multiple endocrine glands (e.g., adrenal, thyroid, pancreatic islets) in the same patient/family.
▶Why does aldosterone deficiency cause hyperkalemia and hyponatremia?
Aldosterone normally promotes Na⁺ reabsorption and K⁺ excretion; its loss causes salt-wasting hyponatremia and potassium retention.
▶What is the cornerstone of long-term treatment for Addison's disease?
Lifelong replacement of glucocorticoid (cortisol) and mineralocorticoid (aldosterone) hormones.
▶Why is the patient's low blood pressure (96/68) expected in Addison's disease?
Aldosterone deficiency causes volume depletion and salt-wasting, lowering blood pressure.
▶What is the most common cause of Addison's disease in developed countries?
Autoimmune adrenalitis (autoimmune destruction of the adrenal cortex).
▶What lab pattern of sodium, potassium, and glucose is classic for Addison's disease?
Low sodium, high potassium, and low glucose.
▶How should a suspected Addisonian crisis be managed acutely?
Immediate IV hydrocortisone, IV fluids/saline to correct volume and hyponatremia, and treatment of hyperkalemia and hypoglycemia.