Oncocytic adrenocortical tumour presenting as an incidentaloma: a diagnostic challenge.

Oncocytic adrenocortical neoplasms are a rare histopathological subtype of adrenal tumours which are usually benign and, if malignant, are less likely to metastasise. We report a case of a non-functioning oncocytic adrenocortical tumour, identified incidentally in a middle-aged woman. It was initially reported as a left-sided 3.5×3.4×5.6 cm adrenal adenoma. It however increased in size to 5.4×4.0×4.3 cm on follow-up scans. Subsequent review of the scans revealed an indeterminate lesion with a precontrast density of 30 Hounsfield units, an absolute washout of 42.6% and a relative washout of 28.6%. As a result, laparoscopic left adrenalectomy was performed. Histology confirmed oncocytic adrenocortical carcinoma when using the Lin-Weiss-Bisceglia system, though it was deemed benign when using the Helsinki scoring system. There has been no evidence of recurrence to date. This case highlights the potential pitfalls in the diagnosis of oncocytic neoplasms and the increased specificity of the Helsinki score in assessing metastatic potential.

A recessive PRDM13 mutation results in congenital hypogonadotropic hypogonadism and cerebellar hypoplasia.

The positive regulatory (PR) domain containing 13 (PRDM13) putative chromatin modifier and transcriptional regulator functions downstream of the transcription factor PTF1A, which controls GABAergic fate in the spinal cord and neurogenesis in the hypothalamus. Here, we report a recessive syndrome associated with PRDM13 mutation. Patients exhibited intellectual disability, ataxia with cerebellar hypoplasia, scoliosis, and delayed puberty with congenital hypogonadotropic hypogonadism (CHH). Expression studies revealed Prdm13/PRDM13 transcripts in the developing hypothalamus and cerebellum in mouse and human. An analysis of hypothalamus and cerebellum development in mice homozygous for a Prdm13 mutant allele revealed a significant reduction in the number of Kisspeptin (Kiss1) neurons in the hypothalamus and PAX2+ progenitors emerging from the cerebellar ventricular zone. The latter was accompanied by ectopic expression of the glutamatergic lineage marker TLX3. Prdm13-deficient mice displayed cerebellar hypoplasia and normal gonadal structure, but delayed pubertal onset. Together, these findings identify PRDM13 as a critical regulator of GABAergic cell fate in the cerebellum and of hypothalamic kisspeptin neuron development, providing a mechanistic explanation for the cooccurrence of CHH and cerebellar hypoplasia in this syndrome. To our knowledge, this is the first evidence linking disrupted PRDM13-mediated regulation of Kiss1 neurons to CHH in humans.

Paradoxical deterioration in seizure control due to anticonvulsant-induced hypocalcaemia.

Hepatic cytochrome P450 enzyme induction is associated with certain antiepileptic drugs (AEDs) and may result in hypocalcaemia secondary to vitamin D deficiency. We report a case of a 44-year-old man with a history of epilepsy, who presented with breakthrough seizures after having previously been seizure-free for 11 years. Investigations revealed severe hypocalcaemia with a corrected calcium of 1.7 mmol/L. His phenytoin dose was increased, and he was started on calcium supplementation. He was discharged with a corrected calcium level of 2.05 mmol/L but was readmitted 1 week later with further seizures and a corrected calcium of 1.89 mmol/L. 25-hydroxyvitamin D was low. AED-induced hypocalcaemia was suspected, which had been made paradoxically worse by the increase in phenytoin dose. Alfacalcidol was prescribed and he was switched from phenytoin to levetiracetam with resolution of hypocalcaemia and no further seizures. The authors recommend screening for calcium and vitamin D deficiency in patients on enzyme-inducing AEDs.

Refractory hypocalcaemia complicating metastatic prostatic carcinoma.

A 72-year-old man with a background of ischaemic heart disease was referred to the accident and emergency department with a 1-week history of worsening dyspnoea and lethargy. A chest X-ray revealed a right-sided lobar pneumonia and a prolonged corrected QT interval was noted on his ECG at presentation. Laboratory investigations confirmed severe hypocalcaemia, significant vitamin D deficiency and relative hypoparathyroidism. A markedly elevated prostate-specific antigen was also identified. Bone scintigraphy demonstrated widespread osteoblastic bone metastases. Severe hypocalcaemia persisted despite treatment and he succumbed after 60 days of hospitalisation.