https://www.nejm.org/doi/full/10.1056/NEJMra1614676
12. Answer: C
Hypogonadism is common in older age men and is most commonly due to functional suppression of sex hormones by chronic disease, medications, and obesity. Hypogonadism as a consequence of testicular or pituitary pathology (organic hypogonadism) is rarer in this age group and occurs in inverse frequency to the level of testosterone, BMI, and degree of comorbidity. First line treatment of functional hypogonadism is lifestyle advice as non‐specific symptoms, including sexual dysfunction, responds well to exercise and weight loss.
Testosterone treatment, with the goal of keeping total serum testosterone within the normal range for a young male can be helpful for some symptoms. Libido and erectile function improved with testosterone in comparison to placebo, but its effect on erectile function is not as significant compared with phosphodiesterase‐5 inhibitors. Poor glycaemic control is better treated with changes to diabetic medications over and above testosterone treatment. Effects on mood, vitality, and physical function are not consistently seen in randomised trials.
Testosterone treatment has some minor effects on muscle mass, fat mass, and bone mineral density, but it is unlikely that these changes are enough to be clinically relevant.
Snyder P, Bhasin S, Cunningham G, Matsumoto A, Stephens‐Shields A, Cauley J et al. Effects of Testosterone Treatment in Older Men. New England Journal of Medicine. 2016;374(7):611–624.
https://www.nejm.org/doi/full/10.1056/NEJMoa1506119
13. Answer: A
Secondary hyperparathyroidism is a common complication in patients with CKD and ESKD. Despite optimised medical treatment, patients with severe secondary hyperparathyroidism may still require parathyroidectomy.
Severe, prolonged, and symptomatic hypocalcaemia is a common post‐operative complication in patients following parathyroidectomy. ‘Hungry Bone Syndrome’ (HBS) is defined as prolonged and severe hypocalcaemia (corrected serum calcium level of 2.1 mmol/L or below) lasting 4 or more days, occurring anytime within 1 month of parathyroidectomy. The measurement of ionised calcium up to 2 to 4 times a day for the first few days postoperatively is preferred to total calcium since it is difficult to predict ionised calcium from total calcium in patients with CKD. Loading with calcitriol pre‐operatively can reduce occurrence of severe hypocalcaemia.
Treatment strategies for hypocalcaemia include giving intravenous calcium, oral calcium, and Vitamin D supplementation such as calcitriol, and even providing haemodialysis treatment using a higher calcium dialysate (1.75 mmol/L) to avoid complications related to hypocalcaemia, such as paraesthesia, tetany, laryngeal spasm, seizures, cardiac arrhythmia, and heart failure.Other biochemical abnormalities which can occur post‐parathyroidectomy include hypomagnesaemia, hypophosphataemia, and hyperkalaemia. The correction of hypomagnesaemia may contribute to correction of the hypocalcaemia. The correction of hypophosphataemia in HBS is usually avoided since phosphate can bind to calcium and worsens hypocalcaemia unless the phosphate level is critically low (<0.16 to 0.32 mmol/L) or hypophosphataemia is associated with severe muscle weakness or heart failure. Hyperkalaemia is more common than hypokalaemia as a complication post‐parathyroidectomy since this group of patients have ESKD and are often oliguric or anuric after chronic dialysis and can be managed post‐operatively with dialysis.
Ho L, Wong P, Sin H, Wong Y, Lo K, Chan S et al. Risk factors and clinical course of hungry bone syndrome after total parathyroidectomy in dialysis patients with secondary hyperparathyroidism. BMC Nephrology. 2017;18(1).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5223390/pdf/12882_2016_Article_421.pdf
14. Answer: A
The tricarboxylic acid (TCA) cycle, also known as the Krebs cycle or citric acid cycle, is important in cell metabolism. The Krebs cycle is a series of chemical reactions in mitochondria used by all aerobic organisms to release stored energy from carbohydrates, fats, and proteins through the oxidation of acetyl‐CoA into adenosine triphosphate (ATP) and carbon dioxide. The cycle also generates precursors of some amino acids and reducing agent (NADH), that can be used in other reactions.
Citrate, a metabolite in the Krebs cycle, has been linked to fatty‐acid synthesis and protein acetylation, which is important for macrophage and dendritic cells activation. Macrophages and dendritic cells play important roles in the innate immune system as the first line of defence against pathogens by producing inflammatory mediators, phagocytosis of pathogens, and releasing chemokines to recruit other inflammatory cells to the site of infection. Dendritic cells are also antigen presenting cells and play an important role in the adaptive immune response.
Itaconate is derived from citrate and has a direct antibacterial effect and is an important immunomodulator.
Williams N, O’Neill L. A Role for the Krebs Cycle Intermediate Citrate in Metabolic Reprogramming in Innate Immunity and Inflammation. Frontiers in Immunology. 2018;9.
https://www.frontiersin.org/articles/10.3389/fimmu.2018.00141/full
15. Answer: C
Multiple endocrine neoplasia (MEN) is characterised by the occurrence of tumours involving two or more endocrine glands. There are four major forms of MEN (Table 4.1), which are autosomal dominant disorders.
Table 4.1 Four major forms of MEN with their characteristics and associated genetic abnormalities.
| Syndrome | Gene mutation | Encoded protein | Clinical criteria |
|---|---|---|---|
| MEN1 | MEN1 (tumour suppressor gene) mutation | Mentin | Parathyroid, pancreatic islet and anterior pituitary tumours |
| MEN2 (MEN2A) | Rearranged during transfection (RET) mutation | Tyrosine kinase receptor | Medullary thyroid carcinoma (MTC) in association with phaeochromocytoma and parathyroid tumours |
| MEN3 (MEN2B) | RET mutation | Tyrosine kinase receptor | MTC and phaeochromocytoma in association with a marfanoid habitus, mucosal neuromas, medullated corneal fibrese and intestinal autonomic ganglion dysfunction, leading to megacolon |
| MEN4 | CDNK1B mutation | Cyclin‐dependent kinase inhibitor |
Parathyroid and anterior pituitary tumours in possible association with tumours of the adrenals, kidneys, and reproductive organs
|