Pathophysiology
P-I-16. Menopause & osteoporosis, Case 4
閉経と骨粗鱬症 症例4
A 52-year-old woman underwent a medical check-up because of palpitation, paroxysmal erythema (skin flush) and increased perspiration. Her anamnesis includes miscarriage (24 years ago) and deep vein thrombosis (20 years ago), but the initially suspected diagnosis of antiphospholipid syndrome was not confirmed by subsequent lab tests. She was diagnosed with Graves-Basedow disease at age 41, which was treated with radioiodine therapy; since then she has been receiving levothyroxine substitution. She is on a special diet due to her gluten sensitive enteropathy. Her last menstrual period was 3 years ago. Both her mother and her grandmother had had breast tumors.
Physical examination:
- height: 165 cm
- weight: 57 kg
- blood pressure: 135/88 Hgmm
Blood:
- Total cholesterol: 7 mmol/L
- ASAT: 40 U/L
- ALAT: 35 U/L
- TSH level: 3.5 mU/L (normal)
- FSH: 50 U/L (high)
- LH: 50 U/L (high)
Urine (collected, 24-hours):
- Cortisol: 12 µg (normal)
- 5-HIAA: 6 mg (normal)
Key Quotes & What They Tell Us
| Quote / Value | Interpretation |
|---|---|
| “palpitation, paroxysmal erythema (skin flush) and increased perspiration” | Vasomotor symptoms (hot flushes, sweating, palpitations) typical of the menopause |
| “last menstrual period was 3 years ago” | Clinically postmenopausal |
| FSH 50 U/L (high); LH 50 U/L (high) | Hypergonadotropic hypogonadism — loss of ovarian oestrogen removes negative feedback → high gonadotropins (confirms menopause) |
| TSH 3.5 mU/L (normal) on levothyroxine after radioiodine for Graves’ | Currently euthyroid — excludes recurrent hyperthyroidism as the cause of flushing/palpitations |
| Total cholesterol 7 mmol/L (high) | Oestrogen loss → unfavourable lipid profile after menopause |
| 24-h urinary cortisol and 5-HIAA normal | Excludes phaeochromocytoma/carcinoid and Cushing’s as mimics of the vasomotor symptoms |
| Mother and grandmother had breast tumours | Family history relevant to any hormone-replacement decision |
Key Points
- Diagnosis: Menopause (physiological), confirmed by elevated FSH/LH with vasomotor symptoms.
- Pathophysiology: Ovarian failure → oestrogen deficiency → loss of feedback (high FSH/LH) and thermoregulatory instability (hot flushes).
- Key differential: Palpitations/sweating could suggest hyperthyroidism, but a normal TSH on levothyroxine rules it out; normal cortisol and 5-HIAA exclude other endocrine mimics.
- Associated risks: Post-menopausal dyslipidaemia (raised cholesterol) and bone loss.
- Relevant history: Treated Graves’ disease, coeliac disease, prior DVT, and a family history of breast cancer — all important when weighing hormone-replacement therapy.
一問一答
▶In the Case 4 patient (hot flushes, high FSH/LH, last period 3 years ago), what is the diagnosis?
Physiological menopause, confirmed by elevated FSH/LH with vasomotor symptoms.
▶What is the pathophysiology of menopause?
Ovarian failure causes estrogen deficiency, which removes negative feedback (raising FSH/LH) and destabilizes thermoregulation (hot flushes).
▶Why are FSH and LH elevated in menopause?
Loss of ovarian estrogen removes negative feedback on the pituitary, causing hypergonadotropic hypogonadism (high FSH/LH).
▶What vasomotor symptoms are typical of menopause in Case 4?
Palpitations, paroxysmal skin flushing (hot flushes), and increased perspiration.
▶Why does a normal TSH on levothyroxine matter in Case 4?
It confirms the patient is euthyroid, excluding recurrent hyperthyroidism as the cause of the palpitations and flushing.
▶Why were 24-hour urinary cortisol and 5-HIAA measured in Case 4?
To exclude pheochromocytoma/carcinoid (5-HIAA) and Cushing's (cortisol) as mimics of the vasomotor symptoms; both were normal.
▶Why is total cholesterol elevated (7 mmol/L) in Case 4?
Estrogen loss after menopause causes an unfavorable lipid profile (postmenopausal dyslipidemia).
▶Why is the family history of breast cancer relevant in Case 4?
It is important when weighing hormone-replacement therapy, which can increase breast cancer risk.
▶What major health risks increase after menopause?
Osteoporosis (bone loss) and cardiovascular disease from dyslipidemia, due to estrogen deficiency.
▶How do prior DVT and treated Graves' disease affect HRT decisions in Case 4?
A prior DVT raises thrombotic risk, making estrogen-containing HRT relatively contraindicated; her thyroid history must also be considered.
▶What is hypergonadotropic hypogonadism?
Gonadal failure (low sex hormones) with elevated gonadotropins (FSH/LH) due to loss of feedback inhibition — the hormonal picture of menopause.
▶Why can palpitations and sweating be mistaken for hyperthyroidism in Case 4?
Both menopause and hyperthyroidism produce adrenergic-type symptoms; thyroid testing is needed to distinguish them.
▶How is menopause defined clinically?
Permanent cessation of menstruation, confirmed retrospectively after 12 consecutive months of amenorrhea.
▶What is the mechanism of menopausal hot flushes?
Estrogen withdrawal destabilizes the hypothalamic thermoregulatory center, narrowing the thermoneutral zone and triggering vasodilation and sweating.
▶Why is coeliac disease (gluten-sensitive enteropathy) relevant to bone health here?
Malabsorption from coeliac disease can impair calcium/vitamin D absorption, adding to postmenopausal bone-loss risk.
▶What benefits and risks must be balanced when considering HRT for menopause?
Benefits: relief of vasomotor symptoms and bone protection. Risks: thromboembolism and breast cancer, especially with personal/family risk factors.
▶Why does estrogen deficiency worsen the lipid profile?
Estrogen normally lowers LDL and raises HDL; its loss raises total/LDL cholesterol, increasing cardiovascular risk.
▶Why was antiphospholipid syndrome considered in her past history?
Because of her prior miscarriage and DVT, though subsequent lab tests did not confirm it.
▶Why are normal cortisol and 5-HIAA important for confirming menopause as the cause?
They exclude endocrine tumors (Cushing's, carcinoid, pheochromocytoma) that mimic flushing/palpitations, leaving menopause as the explanation.
▶What is the average age of natural menopause?
Around 51 years (typically early 50s).