Differentials
Hyperparathyroidism-jaw tumour syndrome
SIGNS / SYMPTOMS
Strong family history of hyperparathyroidism-jaw tumour syndrome.
Parathyroid carcinoma develops in 10% to 15% of affected patients.
INVESTIGATIONS
Raised calcium levels (can be in the range of 3.25 to 3.5 mmol/L [13-14 mg/dL]).
Genetic testing for HRPT2 gene germline mutations.[58]
Familial isolated hyperparathyroidism
SIGNS / SYMPTOMS
A differential diagnosis of MEN1/2, resulting in isolated hyperparathyroidism without any other endocrinopathy. It is an autosomal dominant condition and can be considered a MEN1 variant, as it can result from mutations of the MEN1 gene (other genes have also been identified). The MEN1 mutations that cause familial isolated hyperparathyroidism (FIHP) tend to be missense mutations, whereas the MEN1 syndrome tends to be associated with nonsense mutations. Some families with MEN1 mutations appear to develop limited clinical manifestations. For example, some kindreds develop FIHP as the only endocrinopathy. MEN1 mutations were reported in 42 FIHP kindreds.[3]
INVESTIGATIONS
Genetic testing for MEN1 gene mutations. However, this may be insufficiently sensitive, meaning patients require continued monitoring for late appearances of non-parathyroid tumours characteristic of MEN1.
Sporadically occurring primary hyperparathyroidism
SIGNS / SYMPTOMS
Age of onset for sporadic cases is up to 30 years later than for MEN1.[59]
INVESTIGATIONS
MEN screening (performed if unusual features exist, e.g., family history, young age at presentation.)
Familial hypocalciuric hypercalcaemia
SIGNS / SYMPTOMS
Positive family history.
Generally asymptomatic.
INVESTIGATIONS
Calcium clearance to creatinine clearance ratio <0.01 (tested when vitamin D replete and in the absence of interfering medications, such as thiazide diuretics).
Lifelong elevated serum calcium levels in index cases and family members.
Parathyroid hormone may be elevated.
Isolated familial pituitary tumours
SIGNS / SYMPTOMS
Usually familial somatotropinomas that are distinguished from sporadic acromegaly by positive family history.[60]
INVESTIGATIONS
Genetic testing may reveal mutations in aryl hydrocarbon receptor-interacting protein genes (found in some families with isolated pituitary tumours).
Carney's complex
SIGNS / SYMPTOMS
Spotty skin pigmentation, cardiac myxomas, and pigmented adrenal cortical hyperplasia.[61]
Abnormal skin pigmentation may be the first sign at birth. Lentigines usually assume their characteristic distribution later.
Related cardiac myxoma signs and symptoms include symptoms of right or left ventricular failure, syncope, haemoptysis, Raynaud's phenomenon, murmurs, elevated jugular venous pressures, and/or pyrexia.
INVESTIGATIONS
Genetic testing may reveal inactive mutations in the gene encoding for protein kinase A type 1A regulatory subunits (present in >60% of patients).[62]
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