Endocrine Abstracts

Clinical case: A 23-year-old woman with genetically confirmed pseudohypoparathyroidism type 1b (PHP1b) reported a one-month history of progressive bilateral cervical lymphadenopathy at her most recent outpatient visit. This was associated with night sweats and a dry cough, but no weight loss, haemoptysis or recent foreign travel. Clinical examination revealed widespread non-tender cervical and inguinal lymphadenopathy with no hepatosplenomegaly. An expedited ultrasound guided lymph node biopsy was arranged following discussion with haematology.

Investigations: Lymphocytosis 5.2 × 10^9/l (1-3) with reactive forms were seen on blood film with normal total white cell, haemoglobin and platelet counts. For her PHP1b, the patient was stable for eighteen months on 1 microgram twice daily alphacalcidol and 2000 units daily vitamin D3, maintaining an adjusted serum calcium just below the lower reference range, with elevated but down trending parathyroid hormone (PTH) and ALP levels; six months prior, adjusted calcium 2.19 (2.20-2.60 mmol/l), phosphate 0.94 (0.8-1.5 mmol/l) with PTH 44.7 (1.6-6.9 pmol/l) and ALP 163 (30-130 u/l), down from 143 pmol/l and 717 u/l respectively, alongside severe symptomatic hypocalcaemia (1.56 mmol/l) at diagnosis two years previously. Normal PTH (5 pmol/l) and ALP (100 units/l) alongside adjusted calcium 2.43 mmol/l, normophosphataemia and preserved renal function were seen at the current visit. Histopathology confirmed t-cell lymphoblastic lymphoma with a high proliferation index; Ki67 90-95%. Diffuse sclerotic bony lesions were seen on staging CT.

Results and treatment: Following an acute presentation with nausea and vomiting, an LDH serum >1800 (0-249 u/l) and an acute severe transaminitis with no other identifiable cause, urgent admission was required to initiate treatment for acute lymphoblastic lymphoma. Day four post first cycle of chemotherapy, adjusted serum calcium was 2.21 mmol/l. Her alphacalcidol and vitamin D3 are being continued at the same doses. The results of serum 1,25-dihydroxy vitamin D3 (1,25(OH)2 D3) and parathyroid hormone related peptide (PTHrP) are awaited.

Discussion: In our patient, normalisation of PTH with mild elevations in serum calcium concurrent with her diagnosis of lymphoma, suggest an ectopic contributor affecting calcium homeostasis. Tumour induced overproduction of 1,25(OH)2 D3 by extrarenal 1a hydroxylation from lymphoma cells or surrounding macrophages is the proposed mechanism. Whilst her end organ resistance to PTH signalling is likely protective against the development of hypercalcaemia and its associated risks, in those with pseudohypoparathyroidism, targeting serum calcium towards the lower end of reference to avoid renal complications is paramount. Elevation of PTH with reduction in serum calcium is expected as remission of malignancy is achieved.