Diabetes and ICH

Q: Diabetes increases the risk of spontaneous intracerebral hemorrhage.

A) True

B) False

Answer: A

Due to inherent underlying pathology of vasculature in diabetes, the risk of spontaneous as well as related to anticoagulation ICH is higher in diabetes.

Unfortunately, anticoagulant-associated intraocular bleed is also higher in patients with diabetic retinopathy.

#hematology

#neurology

#endocrinology

References:

1. Huhtakangas J, Tetri S, Juvela S, et al. Effect of increased warfarin use on warfarin-related cerebral hemorrhage: a longitudinal population-based study. Stroke 2011; 42:2431.

2. Boulanger M, Poon MT, Wild SH, Al-Shahi Salman R. Association between diabetes mellitus and the occurrence and outcome of intracerebral hemorrhage. Neurology 2016; 87:870.

3. Nentwich MM, Ulbig MW. Diabetic retinopathy - ocular complications of diabetes mellitus. World J Diabetes. 2015 Apr 15;6(3):489-99. doi: 10.4239/wjd.v6.i3.489. PMID: 25897358; PMCID: PMC4398904.

DPP-4 with metformin

Q: Dipeptidyl peptidase 4 (DPP-4) inhibitors should not be combined with metformin to avoid the risk of severe hypoglycemia.

A) True

B) False

Answer: B

DPP-4 inhibitors, the most popular one in the USA is sitagliptin (trade name Januvia), have a low risk of hypoglycemia even when used as an add-on therapy with metformin. The risk of hypoglycemia is higher when combined with insulin or sulfonylureas, which are well-known to cause hypoglycemia by themselves. 

This characteristic of a lower rate of hypoglycemia is particularly useful in patients with chronic renal disease, including patients who require dialysis.

Similarly, good or bad, they have minimal effect on body weight.

#endocrinology

References:

1.  Nauck MA, Meininger G, Sheng D, et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with the sulfonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: a randomized, double-blind, non-inferiority trial. Diabetes Obes Metab 2007; 9:194.

2. Gallwitz B, Rosenstock J, Rauch T, et al. 2-year efficacy and safety of linagliptin compared with glimepiride in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, non-inferiority trial. Lancet 2012; 380:475.

3. Arjona Ferreira JC, Corry D, Mogensen CE, et al. Efficacy and safety of sitagliptin in patients with type 2 diabetes and ESRD receiving dialysis: a 54-week randomized trial. Am J Kidney Dis 2013; 61:579.

Pentad of Graves' disease

Q: What is the pentad of Graves' disease?

Answer: A full-blown ideal Graves' disease usually consists of five features:

1. Hyperthyroidism
2. Goiter
3. Oorbitopathy
4. Dermopathy
5. Tachycardia

Other features may also be present, including heat intolerance, tremor, palpitations, anxiety, weight loss despite a normal or increased appetite, increased bowel frequency, and shortness of breath. Skin exam may have some remarkable and striking onycholysis, softening of the nails, hyperpigmentation, pruritus and hives, vitiligo, alopecia areata, and thinning of the hair.

A large number of patients may not have all of these features overtly. Diagnosis is based on clinical signs and symptoms and laboratory work-up.

Graves' disease, by definition, is an autoimmune disease. It is caused by thyroid-stimulating hormone (TSH, thyrotropin) receptor antibodies (TRAb) that activate the receptor, thereby stimulating thyroid hormone synthesis and secretion, as well as thyroid growth (diffuse goiter).

#endocrinology

#clinical-exam

References:

1. Toro-Tobon D, Stan MN. Graves’ Disease and the Manifestations of Thyrotoxicosis. [Updated 2024 Sep 24]. In: Feingold KR, Adler RA, Ahmed SF, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK285567/

2. Lee SY, Pearce EN. Hyperthyroidism: A Review. JAMA. 2023 Oct 17;330(15):1472-1483. doi: 10.1001/jama.2023.19052. PMID: 37847271; PMCID: PMC10873132.

3. Davies TF, Andersen S, Latif R, Nagayama Y, Barbesino G, Brito M, Eckstein AK, Stagnaro-Green A, Kahaly GJ. Graves' disease. Nat Rev Dis Primers. 2020 Jul 2;6(1):52. doi: 10.1038/s41572-020-0184-y. PMID: 32616746.

Hydrocortisone and Mineralocorticoid activity

Q: What is the ratio of Mineralocorticoid: Glucocorticoid activity in hydrocortisone? - select one

A) 1:1

B) 1:2

C) 1:3

D) 1:4

Answer: A

Hydrocortisone continues to be the favored drug in ICUs for stress dose steroids in sepsis and other clinical situations where adrenal insufficiency is suspected. This is due to a 1:1 ratio of mineralocorticoid: glucocorticoid activity.

Dexamethasone has the least, rather negligible, mineralocorticoid activity.

#pharmacology

#endocrinology

References:

1. Ekman B, Quinkler M, Zhang P, Isidori AM, Murray RD, Wahlberg J; EU-AIR investigators. Mineralocorticoid effects of fludrocortisone and hydrocortisone in primary adrenal insufficiency: EU-AIR patient data. J Endocrinol Invest. 2025 Oct;48(10):2381-2392. doi: 10.1007/s40618-025-02657-7. Epub 2025 Sep 6. PMID: 40913682; PMCID: PMC12518465.

2. Venkatesh B, Cohen J. Hydrocortisone in Vasodilatory Shock. Crit Care Clin. 2019 Apr;35(2):263-275. doi: 10.1016/j.ccc.2018.11.005. Epub 2019 Jan 28. PMID: 30784608.

3. Sattar NA, Gaw A. Mineralocorticoid effects of high dose hydrocortisone. BMJ. 1995 Jul 22;311(6999):260. doi: 10.1136/bmj.311.6999.260b. PMID: 7627063; PMCID: PMC2550311.

chloride in adrenal insufficiency

Q: Patients with adrenal insufficiency tend to have? - select one

A) Hyperchloremia

B) Hypochloremia

Answer: A

Adrenal insufficiency, as defined by mineralocorticoid deficiency, causes hyperkalemia and hyperchloremic acidosis. 

Mechanism of action: The loss of aldosterone reduces hydrogen ion excretion in the renal collecting duct, leading to hyperchloremic normal anion gap metabolic acidosis. 

Other imbalances that may occur

• Hyponatremia 
• hypercalcemia (though rare)
• hypoglycemia

#electrolytes

#endocrinology

References:

1. Sagar N, Lohiya S. A Comprehensive Review of Chloride Management in Critically Ill Patients. Cureus. 2024 Mar 6;16(3):e55625. doi: 10.7759/cureus.55625. PMID: 38586759; PMCID: PMC10995984.

2. Kromah F, Tyroch A, McLean S, Hughes H, Flavin N, Lee S. Relative adrenal insufficiency in the critical care setting: debunking the classic myth. World J Surg. 2011 Aug;35(8):1818-23. doi: 10.1007/s00268-011-1126-3. PMID: 21533963; PMCID: PMC7101698.

3. Fries C, Fenske W. Elektrolytentgleisungen unter endokrinologischen Gesichtspunkten [An Endocrinological Perspective on Electrolyte Imbalances]. Dtsch Med Wochenschr. 2025 Aug;150(15):883-889. German. doi: 10.1055/a-2318-7580. Epub 2025 Jul 21. PMID: 40690933.

Eye and Semaglutide

Q: Ischemic optic neuropathy due to semaglutide is?

A) reversible

B) irreversible

Answer: B

The last decade has seen a tremendous rise in the use of Glucagon-like peptide 1 (GLP-1)-based therapies, which include GLP-1 receptor agonists, dual-acting GLP-1 and glucose-dependent insulinotropic polypeptide [GIP] receptor agonists. Unfortunately, the improper use of semaglutide has skyrocketed due to its property of quick weight loss.

Non-arteritic ischemic optic neuropathy (NAION) is a dreaded side effect of semaglutide, as it causes irreversible vision loss. Any patient who experiences worsening vision while taking semaglutide should discontinue it and consult their physician immediately.

# endocrinology

# ophthalmology

#pharmacology

References:

1. Grauslund J, Taha AA, Molander LD, et al. Once-weekly semaglutide doubles the five-year risk of nonarteritic anterior ischemic optic neuropathy in a Danish cohort of 424,152 persons with type 2 diabetes. Int J Retina Vitreous 2024; 10:97.

2. Hathaway JT, Shah MP, Hathaway DB, et al. Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide. JAMA Ophthalmol 2024; 142:732.

3. Natividade GR, Spiazzi BF, Baumgarten MW, et al. Ocular Adverse Events With Semaglutide: A Systematic Review and Meta-Analysis. JAMA Ophthalmol 2025; 143:759.

Other labs in hyperthyroidism

Q; In patients with hyperthyroidism, serum total, low-density (LDL), and high-density lipoprotein (HDL) cholesterol tends to be? - select one

A) higher

B) lower

Answer: B

It is always interesting and a good clinical and academic exercise to look for nonspecific laboratory findings in patients with hyperthyroidism. These patients usually have

• lower total, LDL, and HDL cholesterol (due to high sympathathetic activity)
• increased red blood cell (RBC) mass*
• increased plasma volume*
• higher alkaline phosphatase level^
• higher osteocalcin concentrations^

*RBC mass is increased, but the plasma volume is even more increased, showing up as a normochromic, normocytic anemia

^ due to increased bone turnover

#endocrinology

#laboratory-medicine

References: 

1. O'Brien T, Katz K, Hodge D, et al. The effect of the treatment of hypothyroidism and hyperthyroidism on plasma lipids and apolipoproteins AI, AII and E. Clin Endocrinol (Oxf) 1997; 46:17.

2. Dorgalaleh A, Mahmoodi M, Varmaghani B, Kiani Node F, Saeeidi Kia O, Alizadeh Sh, Tabibian Sh, Bamedi T, Momeni M, Abbasian S, Kashani Khatib Z. Effect of thyroid dysfunctions on blood cell count and red blood cell indice. Iran J Ped Hematol Oncol. 2013;3(2):73-7. Epub 2013 Apr 22. PMID: 24575274; PMCID: PMC3915449.

3. Kumeda Y, Inaba M, Tahara H, Kurioka Y, Ishikawa T, Morii H, Nishizawa Y. Persistent increase in bone turnover in Graves' patients with subclinical hyperthyroidism. J Clin Endocrinol Metab. 2000 Nov;85(11):4157-61. doi: 10.1210/jcem.85.11.6979. PMID: 11095447.

Na in Posm formula

Q: While calculating Effective Plasma Osmolality, particularly in hyperosmotic hyperglycemic nonketotic state (HHNK), which of the sodium (Na) concentrations should be used? - select one

A) Actual measured plasma Na concentration

B) Corrected Na concentration

Answer: A

The formula for effective Plasma osmolality (Posm) is a useful method for diagnosing HHNK, where effective Posm is typically >320 mOsm/kg.

The formula is:

Effective Posm = [2 x Na (mEq/L)] + [glucose (mg/dL) ÷ 18]

The Na concentration used should be the actual measured plasma Na concentration, not the corrected Na concentration with high glucose.

#endocrinology

#electrolytes

#metabolism

References:

1. Rasouli M. Basic concepts and practical equations on osmolality: Biochemical approach. Clin Biochem. 2016 Aug;49(12):936-41. doi: 10.1016/j.clinbiochem.2016.06.001. Epub 2016 Jun 22. PMID: 27343561.

2. Fazekas AS, Funk GC, Klobassa DS, Rüther H, Ziegler I, Zander R, Semmelrock HJ. Evaluation of 36 formulas for calculating plasma osmolality. Intensive Care Med. 2013 Feb;39(2):302-8. doi: 10.1007/s00134-012-2691-0. Epub 2012 Oct 19. PMID: 23081685.

C-peptide level in factitious hypoglycemia

Q: A 22-year-old college student residing in a dorm presented to the ED for the third time in a month with hypoglycemia without a history of diabetes. There is a suspicion of factitious hypoglycemia, as the roommate showed suspicion that he may be using his insulin. C-peptide level is sent. In the event of factitious hypoglycemia, the C-peptide level is supposed to be? select one

A) < 0.2 nmol/L

B) ≥0.2 nmol/L 

Answer A

Two tests that rule out factitious hypoglycemia or accidental or surreptitious insulin administration are

• C-peptide level less than 0.2 nmol/L, and
• plasma proinsulin level less than 5 pmol/L        

C-peptide level ≥0.2 nmol/L and plasma proinsulin ≥5 pmol/L need to be ruled out for an endogenous origin of hyperinsulinism, or other etiologies such as oral hypoglycemic agent-induced hypoglycemia, insulin autoimmune hypoglycemia, and nesidioblastosis/islet cell hypertrophy.

#endocrinology

References:

1. Bonnet-Serrano F, Devin-Genteuil C, Thomeret L, Laguillier-Morizot C, Leguy MC, Vaczlavik A, Bouys L, Zientek C, Bricaire L, Bessiène L, Guignat L, Libé R, Mosnier-Pudar H, Assié G, Groussin L, Guibourdenche J, Bertherat J. C-peptide level concomitant with hypoglycemia gives better performances than insulin for the diagnosis of endogenous hyperinsulinism: a single-center study of 159 fasting trials. Eur J Endocrinol. 2023 Feb 14;188(2):lvad012. doi: 10.1093/ejendo/lvad012. PMID: 36756737.

2. Awad DH, Gokarakonda SB, Ilahi M. Factitious Hypoglycemia. [Updated 2023 Sep 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK542310/

Temperature in Myxedema coma

Q: The severity of the hypothermia is related to mortality in Myxedema coma.

A) True

B) False

Answer: A

The seven cardinal signs, though not all may be present in myxedema coma, are:

1. Decreased mental status
2. Hypothermia
3. Bradycardia
4. Hyponatremia
5. Hypoglycemia
6. Hypotension
7. Evidence of Precipitating illness/factor

The severity of the hypothermia is very much related to mortality in severe hypothyroidism, so the level of hypothermia should be established with a reliable temperature-measuring device.

#endocrinology

References:

1. Yamamoto H, Hongo T, Nojima T, Obara T, Kosaki Y, Ageta K, Tsukahara K, Yumoto T, Nakao A, Naito H. Successfully treated case of severe hypothermia secondary to myxedema coma. Acute Med Surg. 2023 Mar 14;10(1):e828. doi: 10.1002/ams2.828. PMID: 36936740; PMCID: PMC10014422.

2. Zhang Y, Chu L, Han H. Myxedema coma: challenges and future directions, a systematic survey and review. Thyroid Res. 2025 Oct 7;18(1):48. doi: 10.1186/s13044-025-00268-1. PMID: 41053871; PMCID: PMC12502585.

Myxedema coma with normothermia

Q: 34 years old female with a known history of hypothyroidism is admitted to the ICU with hypotension, hyponatremia, hypoglycemia, bradycardia, and mental status change. Myxedema coma is suspected. Patient's temperature taken on arrival is reported as normal. The first clinical maneuver should be? - select one

A) Reconsider the diagnosis of myxedema coma

B) Recheck temperature with a reliable thermometer

C) Consult endocrinologist

D) Redraw labs to confirm hyponatremia

E) Request pharmacy to send IV vasopressin STAT

Answer: B

A frankly hypothermic body temperature may not be measured by a regularly used thermometer, and may even falsely be reported as normal. The establishment of the severity of hypothermia (choice B) is essential, as the severity of hypothermia is directly proportional to mortality in severe hypothermia.

Reconsidering the diagnosis of myxedema coma (choice A), like all diagnoses, is a prudent thing. Still, it should not bar a physician from starting the crucial time-sensitive treatment and clinical path.

Consulting an endocrinologist (choice C) is the right thing to do, too, but it will take a lot of time and may not be the first step.

Redrawing labs to confirm hyponatremia (choice D) is not required, as labs are usually reliable if they correlate with clinical signs. They can be redrawn after a period of treatment to confirm the improvement of the clinical condition.

Starting Intravenous (IV) vasopressin as a first step (choice E) is not a good choice, as it may even harm the patient, particularly if hyponatremia is present. Hyponatremia in myxedema coma is due to an impairment in free water excretion due to inappropriate excess vasopressin secretion. Concomitant adrenal insufficiency or acute kidney injury may be playing roles too. 

#endocrinology

Referencxes:

1. Mathew V, Misgar RA, Ghosh S, Mukhopadhyay P, Roychowdhury P, Pandit K, Mukhopadhyay S, Chowdhury S. Myxedema coma: a new look into an old crisis. J Thyroid Res. 2011;2011:493462. doi: 10.4061/2011/493462. Epub 2011 Sep 15. PMID: 21941682; PMCID: PMC3175396.

2. Iwasaki Y, Oiso Y, Yamauchi K, et al. Osmoregulation of plasma vasopressin in myxedema. J Clin Endocrinol Metab 1990; 70:534.

3. Liamis G, Filippatos TD, Liontos A, Elisaf MS. MANAGEMENT OF ENDOCRINE DISEASE: Hypothyroidism-associated hyponatremia: mechanisms, implications and treatment. Eur J Endocrinol 2017; 176:R15.

Myxedema madness

Q: What is myxedema madness?

Answer: When myxedema presents with psychotic features, it is called myxedema madness. 

The actual cause of psychosis in these patients is not clear, but concomitant hyponatremia is suspected to be the cause. Seizure is also not uncommon. Progressively, these patients progress to altered consciousness, confusion, lethargy, and obtundation. Focal or generalized seizures may progress to status epilepticus. Lumbar puncture (LP) may reveal elevated protein levels (typically <100 mg/dL).

#endocrinology

#neurology

#psychiatry

References:

1. Westphal SA. Unusual presentations of hypothyroidism. Am J Med Sci 1997; 314:333.

2. Mavroson MM, Patel N, Akker E. Myxedema Psychosis in a Patient With Undiagnosed Hashimoto Thyroiditis. J Am Osteopath Assoc 2017; 117:50.

3. Jansen HJ, Doebé SR, Louwerse ES, et al. Status epilepticus caused by a myxoedema coma. Neth J Med 2006; 64:202.

4. Haupt M, Kurz A. Reversibility of dementia in hypothyroidism. J Neurol 1993; 240:333.

radioactive iodine uptake and thyrotoxicosis factitia

Q; 32 years old female with previous history of Anorexia Nervosa presents with signs and symptoms of thyrotoxicosis. 'Thyrotoxicosis factitia' is highly suspected as no exophthalmos was noted. A low TSH level is found, along with normal free T4 and T3 levels. 24-hour radioiodine uptake ordered. Which of the following may help in confirming the diagnosis?

A) High 24-hour radioiodine uptake

B) Low 24-hour radioiodine uptake

Answer: B

There are many clinical situations, besides the intentional or unintentional intake of exogenous thyroid hormone, that may cause thyrotoxicosis factitia. It includes thyroid cancer, which may require suppressive doses of thyroxine to minimize TSH stimulation of tumor growth, and a higher-than-usual dose prescribed to shrink the thyroid gland. Also, psychiatric disorders are prone to low levels of TSH, and thyroid hormone may be prescribed in combination with antipsychotics. 

Besides history and thyroid hormone levels, the 24-hour radioiodine uptake in the thyroid is nearly absent in patients with exogenous hyperthyroidism due to the suppression of TSH secretion. The only caveat to this confirmatory test is the presence of autonomous functioning thyroid tissue elsewhere in the body, or thyroiditis with the release of preformed hormone from any inflamed gland, such as struma ovarii, and due to iodine-induced hyperthyroidism. 

#endocrinology

#nuclear-medicine

References:

1. Cohen JH 3rd, Ingbar SH, Braverman LE. Thyrotoxicosis due to ingestion of excess thyroid hormone. Endocr Rev 1989; 10:113.

2. Vorasart P, Sriphrapradang C. Factitious thyrotoxicosis: how to find it. Diagnosis (Berl). 2020 May 26;7(2):141-145. doi: 10.1515/dx-2019-0015. PMID: 30927742.

3. Ross DS. Syndromes of thyrotoxicosis with low radioactive iodine uptake. Endocrinol Metab Clin North Am. 1998 Mar;27(1):169-85. doi: 10.1016/s0889-8529(05)70305-4. PMID: 9534035.

Hamburger thyroiditis

Q: What is hamburger thyroiditis?

Answer: The terms hamburger thyroiditis or hamburger hyperthyroidism became popular after community outbreaks of thyrotoxicosis. This interesting form of thyrotoxicosis occurs when thyroid tissue is ingested while eating a hamburger prepared with meat from the neck. If thyroid tissue gets inadvertently removed and ground up with neck muscle in slaughterhouses, it may cause thyrotoxicosis. It is usually a transient form of hypothyroidism, and mimics painless thyroiditis. Interestingly, case reports have described after ingestion of beef or sausage.

#endocrinology

References:

1. Hedberg CW, Fishbein DB, Janssen RS, et al. An outbreak of thyrotoxicosis caused by the consumption of bovine thyroid gland in ground beef. N Engl J Med 1987; 316:993.

2. Kinney JS, Hurwitz ES, Fishbein DB, et al. Community outbreak of thyrotoxicosis: epidemiology, immunogenetic characteristics, and long-term outcome. Am J Med 1988; 84:10.

3. Hendriks LE, Looij BJ. Hyperthyroidism caused by excessive consumption of sausages. Neth J Med 2010; 68:135.

4. Parmar MS, Sturge C. Recurrent hamburger thyrotoxicosis. CMAJ 2003; 169:415.

DKA and lipids

Q: The plasma triglyceride level in patients with Diabetic ketoacidosis (DKA) and Hyperglycemic Hyperosmolar State (HHS) would be? - select one

A) lower

B) elevated

Answer: B

DKA or HHS can cause hyperlipidemia to the point where the serum appears lactescent. This effect is more pronounced in DKA. Levels fall back to normal with insulin therapy.

This occurs due to Lipolysis secondary to insulin deficiency. It also causes elevation of lipolytic hormones such as catecholamines, growth hormone, corticotropin [ACTH], and glucagon. Insulin is the most potent anti-lipolytic hormone; therefore, if DKA or HHS is not treated promptly, ongoing lipolysis releases glycerol and free fatty acids, which cause insulin resistance at both the peripheral and hepatic levels, and serve as substrates for ketoacid generation in hepatocyte mitochondria. In severe cases, it may require plasma exchange.

Another implication of this hyperlipidemia is pseudohyponatremia and/or pseudohyperchloremia. 

#endocrinology

References:

1. Chreitah A, Hijazia K, Doya L, Salloum A. Severe dyslipidemia associated with diabetic ketoacidosis in newly diagnosed female of type 1 diabetes mellitus. Oxf Med Case Reports. 2021 Oct 26;2021(10):omab036. doi: 10.1093/omcr/omab036. PMID: 34729187; PMCID: PMC8557415.

2. Weidman SW, Ragland JB, Fisher JN Jr, et al. Effects of insulin on plasma lipoproteins in diabetic ketoacidosis: evidence for a change in high density lipoprotein composition during treatment. J Lipid Res 1982; 23:171.

3. Huang S, Song F, Gao K, Song Y, Chen X. Plasma exchange treatment of a diabetic ketoacidosis child with hyperlipidemia to avoid pancreatitis: a case report. Front Pediatr. 2024 Jun 5;12:1280330. doi: 10.3389/fped.2024.1280330. PMID: 38903770; PMCID: PMC11188404.

HbA1C in ESRD

Q: In end-stage renal Disease (ESRD) patients, Glycated hemoglobin (A1C) is a better reflection of blood glucose control than daily or continuous self-monitoring of blood glucose (SMBG).

A) True

B) False

Answer: B 

In ESRD or patients with high grade renal failure, i.e., estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m2, the linear relationship between the average glucose and A1C gets unreliable due to altered red cell turnover, especially in patients who are getting treated with erythropoiesis-stimulating agents (ESAs). Rapid red cell turnover means higher younger red cells, and so the falsely low A1C values. The case was reversed in the past due to analytical interference from carbamylated hemoglobin, which formed due to the elevated urea concentrations. But most labs have abandoned old assay machines.

Another twist to the erratic value of HbA1C comes in patients who are on hemodialysis, as repetitive exposure of the patient's RBCs tends to give high HbA1C levels in even non-diabetic patients.

Either daily glucose monitoring (fingersticks) or continuous glucose monitoring is a better indicator of diabetes control in high-grade or ESRD patients.

#nephrology

#endocrinology

#laboratory-medicine

References:

1. Bloomgarden Z, Handelsman Y. How does CKD affect HbA1c? J Diabetes. 2018 Apr;10(4):270. doi: 10.1111/1753-0407.12624. Epub 2017 Dec 21. PMID: 29124865.

2. Wang X, Peesapati SK, Renedo MF, Moktan S. Hemoglobin A1c levels in non-diabetic patients with end-stage renal disease (ESRD) receiving hemodialysis. J Endocrinol Invest. 2004 Sep;27(8):733-5. doi: 10.1007/BF03347514. PMID: 15636425.

3. Coelho S. What is the Role of HbA1c in Diabetic Hemodialysis Patients? Semin Dial. 2016 Jan-Feb;29(1):19-23. doi: 10.1111/sdi.12408. Epub 2015 Jul 2. PMID: 26138753.

WBC in DKA

Q: Leukocytosis in Diabetic ketoacidosis (DKA) is proportional to the degree of ketonemia.

A) True

B) False

Answer: A (True)

DKA is classically a triad of

• hyperglycemia
• anion gap metabolic acidosis
• ketonemia

Normoglycemic DKA may also occur.

Although leukocytosis is not a very commonly seen marker in DKA, it is usually proportional to the degree of ketonemia. Leukocytosis occurs due to hypercortisolemia and increased catecholamine secretion, which correlates with ketonemia.

Said that many times, infection may precipitate DKA, and in such cases, a white blood cell count over 25,000/microL or more than 10 percent bands should increase the suspicion of underlying sepsis.

#endocrinology

#ID

References:

1. Stentz FB, Umpierrez GE, Cuervo R, Kitabchi AE. Proinflammatory cytokines, markers of cardiovascular risks, oxidative stress, and lipid peroxidation in patients with hyperglycemic crises. Diabetes 2004; 53:2079.

2. Nematollahi LR, Taheri E, Larijani B, et al. Catecholamine-induced leukocytosis in acute hypoglycemic stress. J Investig Med 2007; 55:S262.

3. Slovis CM, Mork VG, Slovis RJ, Bain RP. Diabetic ketoacidosis and infection: leukocyte count and differential as early predictors of serious infection. Am J Emerg Med 1987; 5:1.

Testosterone Replacement Therapy and Klinefelter Syndrome

Q: A 28-year-old male with known Klinefelter syndrome and previous Deep Venous Thromboses (DVTs) is admitted to ICU with pulmonary embolism (PE) after missing his anticoagulation tablets while on vacation. One of the permanent treatments besides anticoagulation in this clinical scenario is tеѕtοѕtеrone therapy.

A) True

B) False

Answer: A

Although tеѕtοѕtеrone therapy is conventionally associated with a higher risk of DVTs, in Klinefelter syndrome, it reduces the risk.

Overall, patients with Klinefelter syndrome are at higher risk of ischemic heart disease, mitral valve prolapse, lower extremity varicose veins, venous stasis ulcers, DVT, PE, increased body fat, hypertension, dyslipidemia, and abnormal glucose homeostasis.

The increased risk of DVT and PE is due to impaired fibrinolysis secondary to supernumerary X chromosome(s). Tеѕtοѕtеrone therapy reduces the thrombotic risk by decreasing serum fibrinogen and body fat in hypogonadal mаlеѕ.

#genetics

#cardiology

#hematology

#metabolism

References:

1. Gravholt CH, Chang S, Wallentin M, et al. Klinefelter Syndrome: Integrating Genetics, Neuropsychology, and Endocrinology. Endocr Rev 2018; 39:389.

2. Chang S, Christiansen CF, Bojesen A, et al. Klinefelter syndrome and testosterone treatment: a national cohort study on thrombosis risk. Endocr Connect 2020; 9:34.

3. Chang S, Biltoft D, Skakkebæk A, et al. Testosterone treatment and association with thrombin generation and coagulation inhibition in Klinefelter syndrome: A cross-sectional study. Thromb Res 2019; 182:175.

4. Chang S, Just J, Skakkebæk A, et al. Testosterone Replacement Therapy in Klinefelter Syndrome-Follow-up Study Associating Hemostasis and RNA Expression. J Clin Endocrinol Metab 2024; 109:978.

CBC and adrenal crisis

Q: Which CBC finding is highly suggestive of Adrenal crisis? (Select one)

A) Neutrophilia

B) Eosinophilia

C) Thrombocytopenia

D) Neutropenia

E) Polycythemia

Answer: B

Hyponatremia, hyperkalemia, metabolic acidosis, and hypoglycemia may be present along with anemia and lymphocytosis, but eosinophilia with said serum chemistry findings is highly suggestive of adrenal crisis.

#endo

#hematology

References:

1. Angelis M, Yu M, Takanishi D, Hasaniya NW, Brown MR. Eosinophilia as a marker of adrenal insufficiency in the surgical intensive care unit. J Am Coll Surg. 1996 Dec;183(6):589-96. PMID: 8957461.

2. Mouloudi E, Katsanoulas C, Vrochides D, Giasnetsova T, Papageorghiou C, Gritsi-Gerogianni N. Eosinophilia as a marker of adrenal insufficiency in critically ill patients with severe septic shock: 1-year prospective study. Crit Care. 2008;12(Suppl 5):P9. doi: 10.1186/cc7042. Epub 2008 Nov 18. PMCID: PMC3300601.

3. Beishuizen A, Vermes I, Hylkema BS, Haanen C. Relative eosinophilia and functional adrenal insufficiency in critically ill patients. Lancet. 1999 May 15;353(9165):1675-6. doi: 10.1016/s0140-6736(99)01346-x. PMID: 10335792

Metformin and vitamin deficiency

Q: Metformin is known to cause the deficiency of which vitamin?

Answer:  Vitamin B12

Metformin and other biguanides reduce the absorption of vitamin B12, particularly in long-term patients. The effect is dose-dependent. The mechanism of action is via altered calcium homeostasis. Intestinal uptake of the vitamin B12-intrinsic factor complex requires calcium. The site of action is the ileum, where metfоrmin affects calcium-dependent membrane action. Fortunately, this action can be easily attenuated or reversed by calcium supplementation.

Diabetic patients are already prone to neuropathy, and in the long term, diabetic users of metformin without calcium supplementation may make it worse.

#pharmacology

#vitamins

#endocrine

References:

1. Ahmed MA, Muntingh G, Rheeder P. Vitamin B12 deficiency in metformin-treated type-2 diabetes patients, prevalence and association with peripheral neuropathy. BMC Pharmacol Toxicol 2016; 17:44.

2. Mazokopakis EE, Starakis IK. Recommendations for diagnosis and management of metformin-induced vitamin B12 (Cbl) deficiency. Diabetes Res Clin Pract 2012; 97:359.

3. Bauman WA, Shaw S, Jayatilleke E, et al. Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin. Diabetes Care 2000; 23:1227.