Tumor-induced osteomalacia - a mystery illness beyond aches, pains, and depression.

Objective. Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by chronic hypophosphatemia and osteomalacia. We present case of a patient with a protracted clinical course of TIO. TIO profoundly affected every aspect of his life with subsequent profound physical and psychosocial disabilities. Method. The review of a complex clinical presentation, serial laboratory investigations, and imaging modalities of a patient with TIO caused by a mesenchymal tumor. Results. The patient presented with chronic lower back pain, severe bilateral leg weakness, and multiple pathological fractures due to severe osteoporosis. His investigations revealed hypophosphatemia, low 1,25 dihydroxyvitamin D, phosphaturia and normal serum calcium, and parathyroid hormone. Elevated fibroblast growth factor 23 (FGF23) confirmed the diagnosis of TIO and 68Ga-DOTATATE-positron emission tomography/computed tomography (PET/CT) imaging correctly identified a tumor in the left femoral head. His clinical features and biochemical abnormalities promptly recovered after successful surgical resection of the mesenchymal tumor. Conclusion. The present case demonstrated the need to extensively investigate causes of generalized bone pain in patients with hypophosphatemia, as TIO is highly curable. Importantly, 68Ga-DOTATATE PET/CT imaging successfully identified the FGF23 producing tumor, which was undetectable by conventional imaging, favoring its early use in suspected TIO presentation. The present report highlights the importance of timely diagnosis of this complex medical condition, aiming to improve general awareness and enable better clinical outcomes for this rare disorder.

Severe Hypothyroidism Complicated by Myopathy and Neuropathy with Atypical Demyelinating Features.

Autoimmune hypothyroidism may result in a wide range of neuromuscular disorders. The frequently observed neurological manifestations of acquired hypothyroidism include mild to moderate myopathy and sensorimotor neuropathy, which usually resolve by clinical and electrophysiological criteria, in adults treated with thyroid hormone replacement. We report a case of a 30-year-old male with severe hypothyroidism secondary to chronic autoimmune thyroiditis who presented with a 2-year history of progressive fatigue, upper and lower limb weakness, myalgia, and intermittent paraesthesia. His neurological exam demonstrated proximal and distal muscle weakness, lower limb areflexia, and relatively intact sensory modalities. The patient's biochemistry revealed unusually and profoundly raised the thyroid stimulating hormone (TSH) level of 405.5 mIU/L (reference range (RR): 0.27-4.2 mIU/L) and creatine kinase (CK) level of 20,804 U/L (RR: 45-250 U/L), while his nerve conduction studies (NCS) demonstrated severe sensorimotor polyneuropathy with both axonal and demyelinating features. Thyroid hormone replacement therapy over the first 3 months resulted in biochemical normalization of his extremely deranged thyroid function tests (TFTs) and CK levels. At 12 months, despite maintaining euthyroidism and noticeable improvement in strength, his nerve conduction studies (NCS) demonstrated the continued absence of distal motor and sensory responses in his lower limbs with only partial improvement in sensory amplitudes and conduction velocities in his upper limbs. This report highlights the potential for severe neuromuscular consequences from advanced and chronic autoimmune hypothyroidism. The patient's myopathy has resolved over a period of three months with prompt normalization of CK levels. Concerningly, the patient achieved significant but incomplete recovery from his mixed axonal and demyelinating neuropathy with residual mild distal weakness and areflexia in his lower limbs and persistent motor and sensory impairments on his NCS. The severity and incomplete resolution of our patient's neurological manifestations emphasize the importance of early diagnosis and the need for prompt therapeutic intervention for hypothyroidism.

Genetics, adaptation to environmental changes and archaic admixture in the pathogenesis of diabetes mellitus in Indigenous Australians.

Indigenous Australians are particularly affected by type 2 diabetes mellitus (T2D) due to both their genetic susceptibility and a range of environmental and lifestyle risk factors. Recent genetic studies link predisposition to some diseases, including T2D, to alleles acquired from archaic hominins, such as Neanderthals and Denisovans, which persist in the genomes of modern humans today. Indo-Pacific human populations, including Indigenous Australians, remain extremely underrepresented in genomic research with a paucity of data examining the impact of Denisovan or Neanderthal lineages on human phenotypes in Oceania. The few genetic studies undertaken emphasize the uniqueness and antiquity of Indigenous Australian genomes, with possibly the largest proportion of Denisovan ancestry of any population in the world. In this review, we focus on the potential contributions of ancient genes/pathways to modern human phenotypes, while also highlighting the evolutionary roles of genetic adaptation to dietary and environmental changes associated with an adopted Western lifestyle. We discuss the role of genetic and epigenetic factors in the pathogenesis of T2D in understudied Indigenous Australians, including the potential impact of archaic gene lineages on this disease. Finally, we propose that greater understanding of the underlying genetic predisposition may contribute to the clinical efficacy of diabetes management in Indigenous Australians. We suggest that improved identification of T2D risk variants in Oceania is needed. Such studies promise to clarify how genetic and phenotypic differences vary between populations and, crucially, provide novel targets for personalised medical therapies in currently marginalized groups.

Improvement in cognitive impairment following the successful treatment of endogenous Cushing's syndrome-a case report and literature review.

BACKGROUND: Endogenous Cushing's syndrome, a rare endocrine disorder, characterised by chronic cortisol hypersecretion, results in neuropsychiatric disturbances and in cognitive deficits, which are only partially reversible after the biochemical remission of the disease. CASE PRESENTATION: We report a case of a woman with a profound cognitive deficit and a gradual functional decline caused by Cushing's disease of at least 10 years duration. The neurosurgical resection of her 2 mm adrenocorticotropic hormone (ACTH) secreting pituitary microadenoma resulted in a successful resolution of the patient's hypercortisolism and a significant recovery of her neurocognitive function. The patient's progress was evaluated using serial clinical observations, functional assessments, Mini-Mental Status exams and through the formal neuropsychological report. Furthermore, the patient's recovery of her neurocognitive function was reflected by a sustained improvement in the patient's specific structural brain abnormalities on radiological imaging. CONCLUSIONS: This report illustrates the importance of early detection and treatment of Cushing's syndrome in order to prevent neurocognitive impairment and neuropsychiatric disorders which are associated with an endogenous cortisol hypersecretion. The long term adverse effects of severe hypercortisolaemia on brain function and the pathophysiological mechanisms responsible for the structural and functional changes in brain anatomy due to glucocorticoid excess are reviewed.

Diabetic ketoacidosis and severe hypertriglyceridaemia as a consequence of an atypical antipsychotic agent.

The atypical antipsychotic agent clozapine, although an effective treatment for schizophrenia, is linked with metabolic adverse effects. We report a case of diabetic ketoacidosis and very severe hypertriglyceridaemia associated with clozapine use, in a patient with type 2 diabetes mellitus, who was successfully treated with continuous insulin infusion and fluids. As clozapine proved to be the most efficacious in controlling the patient's psychotic symptoms, the patient has been continued on clozapine despite its known metabolic side effects. Importantly the patient has achieved satisfactory long-term lipid and glycaemic control. The current recommendations related to the metabolic care for patients treated with atypical antipsychotic agents as well as the mechanisms behind abnormal glucose and lipid regulation with clozapine therapy are discussed.