Familial isolated primary hyperparathyroidism caused by mutations of the MEN1 gene.

BACKGROUND: Familial isolated primary hyperparathyroidism (FIHP) is an autosomal dominant disorder that can represent an early stage of either the multiple endocrine neoplasia type 1 (MEN1) or hyperparathyroidism-jaw tumor (HPT-JT) syndromes; alternatively, the condition can be caused by an allelic variant of MEN1 or HRPT2 (hyperparathyroidism 2 gene), or caused by a distinct entity involving another locus. We have explored these possibilities in a patient with primary hyperparathyroidism, whose mother had a history of renal calculi and primary hyperparathyroidism. INVESTIGATIONS: Serum biochemistry and radiological investigations for primary hyperparathyroidism, MEN1 and HPT-JT, and genetic testing for MEN1 and HRPT2 mutations were undertaken. DIAGNOSIS: FIHP with primary hyperparathyroidism as the sole endocrinopathy due to a previously unreported heterozygous missense germline MEN1 mutation, Tyr351Asn. In addition, another unreported heterozygous missense germline MEN1 mutation, Trp220Leu, was identified in an unrelated male patient with FIHP, whose mother and sister also had primary hyperparathyroidism. DNA from a parathyroid tumor from the sister revealed a loss of heterozygosity in which the mutant allele was retained. This is consistent with Knudson's 'two-hit' model of hereditary cancer and a tumor suppressor role for MEN1 in FIHP. MANAGEMENT: The patient underwent parathyroidectomy and has remained normocalcemic over a follow-up period of 6 years. The other four patients have remained normocalcemic for a follow-up period of 4-15 years following parathyroidectomy. None has developed abnormalities of the MEN1 syndrome, providing further support that FIHP is a distinct genetic variant of the MEN1 syndrome.

Management of a thyroid "incidentaloma" in a patient with cancer: a case report.

The routine use of (18)F-fluorodeoxyglucose-positron emission tomography (PET)/computed tomography scans for staging and assessment of treatment response for cancer has resulted in a large number of thyroid abnormalities being detected as incidental findings ("incidentalomas"). Since most PET/CT scans are performed in the setting of a known nonthyroid malignancy, the need for "incidentalomas" to be further investigated and managed depends on the stage, prognosis, and current treatment plan for the known malignancy. We present a case describing the management of an incidental F-fluorodeoxyglucose-avid thyroid nodule detected in a patient with known metastatic colorectal cancer. On the basis of this case, we discuss the management of incidental PET-detected thyroid nodules in patients with metastatic cancer. Thyroid "incidentalomas" must be seen in the context of the prognosis and treatment plan for the known malignancy.

Management of adrenal incidentaloma: size still matters.

A 56-year-old man was found to have an adrenal incidentaloma on a CT scan of the abdomen. Clinically and biochemically, the mass was not functional. MRI scan revealed a heterogeneously enhancing, T2-hyperintense, right-sided adrenal mass (4.5×6.5 cm). Meta-iodo-benzylguanidine scan was normal, making a diagnosis of pheochromocytoma unlikely. As the mass was larger that 4 cm, it was excised and histopathological examination revealed a rare, composite tumour: benign adrenal adenoma with haemangiomatous and myelolipomatous components. This case highlights the difficulties encountered by a clinician faced with investigating a potentially malignant adrenal mass (based on size) and correlates radiological findings with a rare histopathological specimen.