Makindo Medical Notes

Related Subjects: |Calcium Physiology |Calcitonin |Hypocalcaemia |Hypercalcaemia |Hypomagnesaemia |Hypermagnesaemia |Primary Hyperparathyroidism |Familial hypocalciuric hypercalcaemia (FHH) |Sarcoidosis

It is important to identify patients with Familial Hypocalciuric Hypercalcemia (FHH) to avoid a misdiagnosis of primary hyperparathyroidism and unnecessary parathyroidectomy, as surgery does not correct the elevated calcium in FHH.

About Familial Hypocalciuric Hypercalcemia (FHH)

• Autosomal dominant disorder that causes mild hypercalcemia.
• Characterized by normal or slightly elevated parathyroid hormone (PTH) levels and reduced renal calcium excretion.
• Often misdiagnosed as primary hyperparathyroidism (PHPT), which can lead to unnecessary surgery.

Aetiology

• Most cases of FHH are due to loss-of-function mutations in the CASR gene.
• CASR gene: Encodes the calcium-sensing receptor (CASR), a G-protein-coupled receptor expressed in parathyroid glands and kidneys.
• CASR mutations impair the body’s ability to regulate calcium, leading to hypercalcemia.
• Genetic testing for CASR mutations can confirm FHH diagnosis, especially in ambiguous cases.

Clinical Presentation

• Usually asymptomatic and does not require treatment.
• Rare cases may present with complications such as chondrocalcinosis or acute pancreatitis.

Investigations

• Serum Calcium: Albumin-adjusted calcium levels > 2.6 mmol/L (UK) or mild hypercalcemia.
• Serum Magnesium: Hypermagnesemia is often present.
• Urinary Calcium Excretion: Hypocalciuria (low urinary calcium excretion), a distinguishing feature of FHH.
• PTH Levels: Normal to slightly elevated PTH levels, unlike in PHPT where PTH is often high.

Differential Diagnosis

• Primary Hyperparathyroidism (PHPT): FHH must be differentiated from PHPT to prevent unnecessary parathyroidectomy.

Management

• No Treatment Required: FHH does not generally need treatment as it is asymptomatic.
• Differentiation from PHPT: Essential to prevent unnecessary parathyroid surgery.
• Parathyroidectomy: Ineffective in treating hypercalcemia in FHH.

Distinguishing FHH from PHPT

• Clinical Features: FHH is less likely to present with bone disease, kidney stones, polyuria, or mental status changes compared to PHPT.
• Family History: Hypercalcemia in family members is a strong indicator of FHH due to high penetrance; family screening is a reliable diagnostic tool.
• Urinary Calcium Excretion: FHH is characterized by reduced urinary calcium excretion, unlike PHPT which often shows normal or increased urinary calcium.
• Urinary Cyclic AMP: Normal in FHH, whereas it is elevated in cases of PTH excess (e.g., PHPT).
• Imaging Findings: No parathyroid abnormalities on ultrasonography or radionuclide scanning in FHH.