Endocrine Abstracts

We report a rare case of acute myeloid leukaemia (AML) with high risk cytogenetics and associated hypothalamic diabetes insipidus (HDI).

A 48-year-old female presented to her GP with a 3-month history of tiredness and lethargy. Full blood count revealed haemoglobin 7.0 g/dl (MCV 103fl), white cell count 12.1×10⁹/l (neutrophils 1.33×10⁹/l), platelets 91×10⁹/l; circulating blast cells were evident on the peripheral blood film, and a diagnosis of acute myeloid leukaemia was confirmed by bone marrow biopsy with immunophenotyping demonstrating ‘high risk’ cytogenetics: 45,XX,t(3;3)(q21q26),-7.

On admission to hospital, the patient was noted to have polydipsia and polyuria: average 24 hr fluid intake 8–10 L, with negative balance of around 2 L/day. Routine chemistry: sodium 146 mmol/l, potassium 3.4 mmol/l, urea 0.6 mmol/l, creatinine 78 micromol/l, calcium 2.25 mmol/l, random glucose 7.1 mmol/l, serum and urine osmolalities 296 (NR 280–300) and 56 mosmol/kg respectively. A water deprivation test confirmed the presence of HDI. MRI of the brain revealed loss of the posterior pituitary ‘bright spot’, but no macroscopic evidence of tumour infiltration. Anterior pituitary function tests were entirely normal. The patient’s symptoms were well controlled on desmopressin nasal spray. Unfortunately, despite receiving three different AML chemotherapy regimes, only a short period of remission was achieved, and the patient died 12 months after her initial presentation.

More than seventy cases of HDI in association with AML have been described in the literature, with cytogenetic profiles reported in eighteen subjects: sixteen exhibited chromosome 7 abnormalities (predominantly monosomy 7), eight 3q abnormalities [most commonly: t(3;3)(q21q26) and inv(3;3)(q21q26)] and six combined chromosome 7 and 3 abnormalities as in our case. The pathogenesis of HDI in this setting has not been clearly elucidated: for example, leukaemic infiltration of the hypothalamus/pituitary gland has been observed in only a limited number of cases at post-mortem. Several other molecular mechanisms have been postulated, and these will be discussed in more detail.