Prevalence of adrenal insufficiency among patients with euvolemic hyponatremia

Background: The diagnosis of SIAD requires the exclusion of secondary adrenal insufficiency (AI) among patients with euvolemic hyponatremia (EuVHNa). Studies have suggested about 2.7% to 3.8% of unselected patients presenting to the emergency room with EuVHNa have undiagnosed AI and it is as high as 15% among patients admitted to specialized units for evaluation of hyponatremia. Objective: To study the prevalence of AI among inpatients with EuVHNa in a general medical ward setting Methods: This was a prospective, single centre observational study conducted among general medical inpatients with EuVHNa, defined as patients with a serum Na <135 mmol/L, clinical euvolemia and urine spot sodium >30mmol/L. Additionally patients with recent vomiting, current renal failure, diuretic use and those with uncontrolled hyperglycemia were excluded. Adrenal functions were assessed by a modified ACTH stimulation test called Acton Prolongatum™ stimulation test (APST). A cut off cortisol value of <18mg/dl after 60 minutes of ACTH injection was used to diagnose AI. Results: One hundred and forty-one (141) patients were included and underwent an APST. APST suggested 20/141 (14.2%) had undiagnosed AI. The most common cause of AI (9/20) was secondary AI because of the use of steroids including inhaled steroids and indigenous medicines contaminated with steroids. In 5 (3.5%) patients hypopituitarism was newly diagnosed. Despite primary adrenal insufficiency not commonly presenting as EuVHNa, 2/20 patients had primary adrenal insufficiency. Conclusions: AI is much commoner in our country among inpatients with EuVHNa primarily driven by exogenous steroid use and undiagnosed hypopituitarism.

Trilostane monitoring in canine hyperadrenocorticism: can basal cortisol replace the ACTH stimulation test?

PICO question In dogs with hyperadrenocorticism that are being treated with trilostane, does the measurement of basal cortisol levels have comparable diagnostic performance to the adrenocorticotropic hormone (ACTH) stimulation test? Clinical bottom line Category of research question Diagnosis (effectiveness of treatment monitoring) The number and type of study designs reviewed Four cross-sectional diagnostic accuracy studies were critically reviewed Strength of evidence Weak to moderate (level 2) Outcomes reported There is evidence of moderate strength suggesting that basal cortisol measured at 4–6 hours (and possibly 2–3 hours) post-trilostane can be a good test to exclude adrenal oversuppression, while its use is not suggested for diagnostic confirmation of oversuppression. There is evidence of weak strength that basal cortisol might be helpful for identifying dogs with inadequate adrenal suppression, but cannot be used to rule it out Conclusion Although the evaluation of the available evidence is difficult due to its heterogeneity, there is moderate evidence that a basal cortisol measured at 4–6 hours (and possibly 2–3 hours) post-trilostane dose can be a good test to rule out adrenal oversuppression, but that it cannot be used to definitively diagnose oversuppression. The current evidence suggests that basal cortisol is less useful for identification of inadequate control. Based on one included study, neither ACTH-stimulated nor basal cortisol levels correlate optimally with the actual clinical response of the patient. In this context, it can be concluded that none of the currently used laboratory tests should be used as a sole monitoring tool in dogs with hyperadrenocorticism receiving trilostane and thus, the assessment of the clinical response is of utmost importance How to apply this evidence in practice The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

Case of an unreported genetic variant of salt losing 3-β-hydroxysteroid dehydrogenase deficiency

ABSTRACT Salt losing 3-β-hydroxysteroid dehydrogenase deficiency (HSD3B2) is a rare form of congenital adrenal hyperplasia, seen in &lt;0.5% of cases. We present a 7-year-old male diagnosed with HSD3B2 deficiency, not identified by state newborn screen, due to a novel variant identified in the HSD3B2 gene (c.694C &gt; G; p.His232Asp). This patient was referred to pediatric endocrinology and pediatric biochemical genetics following a fourth hospitalization for emesis and electrolyte derangements including hyponatremia, hyperkalemia, ketoacidosis and hypoglycemia. Endocrinology evaluation yielded elevated 17-hydroxyprogesterone (17-OHP), 17-hydroxypregnenolone (17-OHPreg), dehydroepiandrosterone and adrenocorticotropic hormone (ACTH). ACTH stimulation test indicated flat response. Sequencing of the HSD3B2 revealed a pathogenic variant inherited in trans with the novel c.694C &gt; G (p.His232Asp) variant. The patient was started on daily glucocorticoid and mineralocorticoid replacement and has since had no further adrenal crises.

Cortisol Co-Secretion and Clinical Usefulness of ACTH Stimulation Test in Primary Aldosteronism: A Systematic Review and Biases in Epidemiological Studies

The hypothalamus-pituitary-adrenal (HPA) axis plays an important role in primary aldosteronism. Aldosterone biosynthesis is regulated not only by angiotensin II in the renin-angiotensin-aldosterone system, but also by adrenocorticotropic hormone (ACTH), one of the key components of the HPA axis. Although previous studies have reported cortisol cosecretion in primary aldosteronism, particularly aldosterone-producing adenoma (APA), the clinical relevance of such aldosterone and cortisol cosecretion from APA and hypertension or other metabolic disorders has not been fully established. Several somatic mutations including KCNJ5 and CACNA1D are known to induce autonomous production of aldosterone in APA, and the aldosterone responsiveness to ACTH may vary according to each mutation. The ACTH stimulation test has been reported to be a useful tool to distinguish the subtypes of primary aldosteronism (e.g., unilateral vs bilateral) in some studies, but it has not been commonly applied in clinical practice due to limited evidence. Given the recent advancement of imaging, omics research, and computational approach, it is important to summarize the most updated evidence to disentangle the potential impact of cortisol excess in primary aldosteronism and whether the ACTH stimulation test needs to be considered during the diagnostic process of primary aldosteronism. In this article, we conducted a systematic review of epidemiological studies about (i) cortisol cosecretion in primary aldosteronism and (ii) the ACTH stimulation test for the diagnosis of primary aldosteronism (including subtype diagnosis). Then, we discussed potential biases (e.g., confounding bias, overadjustment, information bias, selection bias, and sampling bias) in the previous studies and introduced some advanced epidemiological/statistical methods to minimize these limitations. A better understanding of biases and epidemiological perspective on this topic would allow us to produce further robust evidence and balanced discussion about the causal mechanisms involving the HPA axis and clinical usefulness of the ACTH stimulation test among patients with primary aldosteronism.

Hyponatraemia due to hypothyroidism: a rare side effect from pomalidomide

Pomalidomide is an immunomodulatory drug used for relapsed and refractory multiple myeloma (RRMM). Hypothyroidism is an uncommon side effect of pomalidomide. We present a 70-year-old male patient with RRMM on daratumumab, pomalidomide and dexamethasone, who presented with 2 weeks of fatigue. Laboratory values showed sodium of 120 mEq/L, plasma osmolarity of 256 mOsm/kg, urine osmolarity of 648 mOsm/kg and urine sodium of 93 mEq/L. Adrenocorticotropic hormone (ACTH) stimulation test was within normal limits. Thyroid-stimulating hormone (TSH) was 88.6 IU/mL (0.380–4.700 IU/mL), total triiodothyronine (TT3) <21 ng/mL (0.8–2 ng/mL), free thyroxine (fT4) 0.10 ng/dL (0.93–1.70 ng/dL) and free triiodothyronine (fT3) <0.5 pg/mL (2.3–4.2 pg/mL). Antithyroid peroxidase antibody was 726 IU/mL (<9 IU/mL). TSH 1 year ago was 2.88 IU/mL and TT3 was 1.06 ng/mL. He was started on levothyroxine with improvement in his symptoms, sodium level and thyroid functions. The most likely culprit was pomalidomide. Checking thyroid functions before and periodically while on pomalidomide is important in screening for this possible side effect.

Occult Adrenal Insufficiency in Renal Amyloidosis Patients

Objective: Systemic amyloidosis may affect many organs, and may cause endocrinologic problems which may result in adrenal insufficiency. However, assessment of adrenocortical reserve is challenging in amyloidosis patients with renal involvement. We aimed to evaluate adrenocortical reserve with various methods of cortisol measurement to determine any occult clinical condition. Methods: Patients with renal amyloidosis and healthy subjects were evaluated in this cross-sectional study. Basal cortisol, corticosteroid-binding globulin (CBG), and albumin levels were measured. Serum free cortisol (cFC) level was calculated. Cortisol response tests performed after ACTH stimulation test (250 μg, intravenously) were evaluated, and free cortisol index (FCI) was calculated. Results: Twenty renal amyloidosis patients, and 25 healthy control subjects were included in the study. Patients and control subjects had similar median serum baseline cortisol levels [258 (126-423) vs 350 (314-391) nmol/L, p=0.169)] whereas patients’ stimulated cortisol levels at the 60th minute were lower [624 (497-685) vs 743 (674-781) nmol/L, p=0.011)]. The 60th-minute total cortisol levels of 8 of the 20 (40%) amyloidosis patients were <500 nmol/L, but only three of these 8 patients had stimulated FCI <12 nmol/mg suggesting an adrenal insufficiency (15%). Conclusion: ACTH stimulation test and cortisol measurements should be considered in renal amyloidosis patients with severe proteinuria to avoid false positive results if only ACTH stimulation test is used. It will be appropriate to evaluate this group of patients together with estimated measurements as FCI.