Elaine Sanderson^1,2, Rui Zhang¹, Simon Carrivick¹
1 QEII PathWest, Nedlands, Western Australia
2 Perth Children's Hospital, Nedlands, Western Australia

This case study presents a 3-year-old child with clinical and biochemical hyperandrogenism. It highlights the role of the laboratory and utility of the 18 LCMS androgen profile in arriving to a rare diagnosis.

Matthew Ruhl^1
1Department of Chemical Pathology, Pathology Queensland

Nitrous oxide, or “laughing gas”, is a commonly used inhaled anaesthetic, usually as an adjunct to other agents.¹ It also has significant potential for recreational misuse, with sequelae including gastrointestinal, neurological, haematological and psychiatric symptoms.¹
I describe a patient with several issues arising from nitrous oxide misuse. A 51-year-old man presented to emergency via ambulance with a reduced GCS of 14 (E₄V₄M₆) following loss of consciousness, with associated bradycardia and hypotension. This was on a background of right hip osteoarthritis for which he had been self-medicating with 6-8 kg of inhaled nitrous oxide daily for over 7 years. He had paraesthesia in both feet.
Normocytic hyperchromic anaemia was noted on the patient’s full blood count, with haemoglobin of 127 g/L (135-180), mean cell volume of 98 fL (80-100) and mean cell haemoglobin of 33.5 pg (27.0-33.0). Serum vitamin B₁₂ was low, at 59 pmol/L (133-680), and serum homocysteine showed marked hyperhomocysteinaemia of 410 μmol/L (<15), with associated elevated serum methylmalonate of 6.6 μmol/L (<0.40).
These results support a frank vitamin B₁₂ deficiency secondary to chronic massive nitrous oxide misuse. The full blood count results did not show the expected macrocytic anaemia, though this is less common than believed.² The patient was treated with 1 mg cyanocobalamin intramuscularly daily, alongside 1 g methionine orally three times a day, both for 14 days; and 100 mg thiamine orally daily, ongoing, with later resolution of paraesthesia. He declined review by alcohol and other drug services and was referred for hip arthroplasty.

Megan Rodney¹, Jenny Butler², Chris Florkowski¹, Simon Thompson¹, Richard King¹, Kelly Rankin¹

¹Canterbury Health Laboratories, Christchurch, NZ

²Department of General Medicine, Christchurch Hospital, Christchurch, NZ

 

A fit and well 47-year-old woman experienced two years of intermittent hyperkalaemia with no obvious underlying cause. Her highest recorded potassium was 8.9 mmol/L (3.5 – 5.2 mmol/L). During this time, she had been asymptomatic with no electrocardiogram (ECG) evidence of hyperkalaemia. She had been referred acutely to the general medicine department on multiple occasions due to hyperkalaemia, but these episodes resolved without treatment.

 

Hyperkalaemia can be a life-threatening condition therefore it is important to treat promptly¹. It is crucial to be certain the hyperkalaemia is authentic and not due to a pre-analytical cause to avoid spurious treatment, as hypokalaemia is also life-threatening. After ruling out the more common causes of hyperkalaemia, the above patient was investigated for familial pseudohyperkalaemia (FP), a benign autosomal dominant condition due to mutations in the ABCB6 gene¹. It results in impairment of passive sodium and potassium permeability in red blood cells which is a temperature dependent ex-vivo phenomenon². Both time and temperature dependent effects with significant potassium ‘leakage’ from red blood cells were observed in the patient compared to the control, supportive of the diagnosis of FP². The patient was found to be heterozygous for a pathogenic variant in ABCB6 c. 1123C>T³. 

 

 

1. Saleh-Anaraki K, Jain A, Wilcox CS, Pourafshar N. Pseudohyperkalemia: Three Cases and a Review of Literature. The American Journal of Medicine [Internet]. 2022 Jul 1;135(7):e150–4. Available from: https://pubmed.ncbi.nlm.nih.gov/35398330/

2. Xiong W, Song J, Yue Z, Pei L, Liu Y, Chen J, et al. Case Report: Familial Pseudohyperkalemia Due to Red Blood Cell Membrane Leak in a Chinese Patient. Frontiers in Medicine. 2022 Mar 17;9.

3. Andolfo I, Alper SL, Delaunay J, Auriemma C, Russo R, Asci R, et al. Missense mutations in the ABCB6 transporter cause dominant familial pseudohyperkalemia. American Journal of Hematology. 2012 Nov 24;88(1):66–72.

Victoria Harraway

Department of Chemical Pathology, Pathology Queensland, Qld, Australia

A 58 year old male presented to the Emergency Department with worsening back pain, following a suspected mechanical injury three weeks prior. He had no past medical history but did report recent poor appetite and 15kg of unintentional weight loss. 

A CT spine showed an acute pathological compression fracture of L2, and heterogenous marrow. Laboratory investigations included a full blood count, which showed normocytic anaemia (Hb 111g/L), and serum chemistry which showed a critically elevated calcium level (4.31 mmol/L, corrected calcium 4.67 mmol/L) and elevated globulin (95g/L). Ionised calcium on the paired blood gas was noted to be normal (1.28 mmol/L).

Serum protein electrophoresis revealed an IgG kappa paraprotein. The patient underwent bone marrow testing and was diagnosed with multiple myeloma. 

Hypercalcaemia is common in multiple myeloma and is used for diagnostic purposes. It is, however, important to note that several cases of pseudohypercalcaemia in multiple myeloma have been reported. Pseudohypercalcaemia occurs due to the binding of calcium by monoclonal immunoglobulins, resulting in an elevation of total serum calcium, with ionised calcium remaining normal. 

This case highlights the importance of ionised calcium measurement in patients with monoclonal gammopathies and multiple myeloma, to prevent erroneous treatment and misclassification of disease. 

Laura Buckton
NSW Health Pathology, Department of Chemical Pathology, Prince of Wales Hospital, Randwick, NSW.

A 37-year-old female presented at 24 weeks gestation with recent onset of acne and hirsutism. Biochemical investigations revealed hyperandrogenism with elevated testosterone (14.9 nmol/L, non-pregnant reference interval: <2 nmol/L) and androstenedione (40.6 nmol/L, non-pregnant reference interval: 0.9 – 7.5 nmol/L), which continued to increase in the second half of her pregnancy. This was her first pregnancy after a history of infertility, and she had been diagnosed with gestational diabetes mellitus. At 39⁺⁴ weeks gestation she delivered a healthy baby girl via caesarean section. Postpartum follow up showed normalisation of her androgen levels, an improvement in her hirsutism, however her acne persisted. This case presentation will discuss the causes, pathogenesis and challenges associated with diagnosing androgen excess during pregnancy.

Anila Hashmi^1,2
1NSW Health Pathology, Liverpool, NSW, Australia; ²University of Technology Sydney, Sydney, NSW, Australia 

Background:
Primary hyperparathyroidism (pHPT) is characterised by excessive secretion of parathyroid hormone (PTH), leading to hypercalcaemia. The treatment of choice is the surgical excision of the hyperfunctioning gland. Noninvasive localisation has limited sensitivity, particularly in patients requiring revision surgery. Although not often thought by laboratorians, selective venous sampling (SVS) for PTH has demonstrated high sensitivity and specificity in localising hyperfunctioning parathyroid tissue. This review evaluated the diagnostic accuracy of SVS for lateralising parathyroid adenomas where non-invasive radiological diagnostic methods yielded inconclusive results.

Case Study:
A 51-year-old female with a complex medical history, including end-stage renal disease, prior thyroidectomy, thymectomy, and multiple parathyroid surgeries, presented with persistently elevated PTH levels and hypercalcaemia. Non-invasive imaging, including bone scans and SPECT-CT, suggested possible adenomas but failed to provide definitive localisation.

Methodology:
SVS was employed to localize the source of elevated PTH levels. A total of 20 samples  were drawn from the internal jugular, subclavian, and brachiocephalic veins, and kept on ice immediately after collection. PTH levels were measured using the Roche Cobas immunoassay. The criterion for a positive result was a significant gradient of PTH levels in the sampled veins compared with peripheral levels.

Results:
SVS identified significantly elevated PTH levels in the left superior and inferior jugular veins, indicating a hyperfunctioning parathyroid adenoma in the left superior parathyroid region. Surgical intervention confirmed the presence of an adenoma, which was successfully excised. Postoperative PTH levels normalized, and the patient experienced substantial improvement in bone pain. Several studies have demonstrated the benefit of SVS before reoperation for hyperparathyroidism. SVS alone has a positive predictive value (PPV) of approximately 75%, which increases to 95% when combined with positive ultrasound findings. Previous studies have reported that combining 4D CT with SVS increased sensitivity from 50% to 95% and accuracy from 55% to 91%. 

Conclusion:
Our case demonstrated the diagnostic value of SVS in localizing parathyroid adenomas, particularly when non-invasive imaging methods yield inconclusive or negative results. SVS is a valuable adjunct to preoperative localisation strategies. Increasing the recognition of the test by laboratorians and clinicians may help with the management of challenging pHPT cases.