Differential Diagnosis of Hot Flashes

Case

In clinic there was an interesting case of a 72 F who experienced severe and debilitating hot flashes triggered by cold water, direct sunlight and some neck movements. This would be followed by multiple hours of chills. She had extensive work up by her GP, endocrinologist and psychiatrist before being referred to the GIM clinic. Differential diagnosis of hot flashes/flushing are presented below.

Differential Diagnosis

Autonomic Mediated 

• thermoregulatory (fever, exercise, heat exposure)
• menopause
• emotional 
• neurologic (masses that compress the third ventricle, diencephalic autonomic epilepsy, cluster headache, spinal cord injury, Parkinson's disease, multiple sclerosis, autonomic hyperreflexia, Frey syndrome, trigeminal neuralgia, migraine, Harlequin syndrome)

Vasodilation Mediated

• rosacea
• medications
• food (spicy, MSG, alcohol)
• carcinoid syndrome
• mastocytosis
• pheochromocytoma
• Medullary thyroid carcinoma
• Serotonin syndrome
• Anaphylaxis
• Pancreatic tumour/VIPoma
• Dumping syndrome or short-gut syndrome
• Sarcoidosis 
• Hyperthyroidism
• Bronchogenic carcinoma
• Androgen deficiency
• Renal cell carcinoma
• Superior vena cava syndrome 

In this patient specifically, post-menopausal vasomotor symptoms were considered. She had a hysterectomy at age 42 and received hormone replacement therapy for 5 years. Her symptoms began around age 60. According to the SWAN study, the median total vasomotor symptom duration is 7.4 years. However our patient has risk factors for longer duration including African ethnicity and psychiatric comorbidity. Furthermore, the DREAMS study which looked at menopausal women >60 years found that those with moderate-severe vasomotor symptoms were more likely to have non-spontaneous menopause. However, symptoms caused by menopause are generally expected to improve with time and not worsen. Therefore additional investigations for rarer causes of flushing were pursued.

References

https://www-uptodate-com.myaccess.library.utoronto.ca/contents/approach-to-flushing-in-adults?search=hot%20flash&source=search_result&selectedTitle=11~150&usage_type=default&display_rank=11

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2110996

https://pubmed.ncbi.nlm.nih.gov/29738420/

A.L.

Workup of Long Covid Symptoms

Intro

Long Covid involves symptoms that develop during or after COVID-19, continue for ≥4 weeks, and are not explained by an alternative diagnosis. In one meta-analysis, it was shown that at 3 months post infection, 6% of patients had symptoms of long covid. Common symptom clusters include:

• fatigue/bodily pain  
• mood/cognitive problems
• respiratory problems
• cardiac problems

Less common persistent physical symptoms include anosmia, joint pain, headache, sicca syndrome, rhinitis, dysgeusia, poor appetite, dizziness (from orthostasis, postural tachycardia, or vertigo), myalgias, insomnia, hoarseness, alopecia, sweating, reduced libido, and diarrhea.

Recommendations for Investigations

It is important to differentiate symptoms following a covid-infection from other well documented post-illness syndromes, including post ICU syndrome, post-viral syndrome and post-hospitalization syndrome. 

General: routine post-covid assessments are not recommended unless patient had a severe covid infection or requests medical attention.

Cardiac: 

12-lead electrocardiogram is recommended for those with cardiac symptoms, and there is a low threshold for ordering TTE. 

Pulmonary:

For all patients who had a pulmonary infiltrate or other abnormality identified on imaging during the acute course of COVID-19 illness, obtain follow-up chest imaging, typically chest radiography, at 12 weeks. For patients with new or progressive symptoms, earlier imaging is indicated. If suspicion is high for another etiology, CT chest is recommended.

For those with persistent, progressive, or new respiratory symptoms and patients recovering from ARDS, pulmonary function tests (PFTs), including spirometry, lung volumes, and diffusion capacity and a six-minute walk test is recommended.

Neuro:

Screen for cognitive impairments with MOCA, and compare with baseline when available.

Imaging is not routinely recommended unless concern for another etiology.

Olfactory/gustatory:

In most cases, these symptoms resolve slowly over several weeks and do not require intervention except for education.

Dermatologic: 

Ask about alopecia and skin lesions (including any residual effects from "COVID toes" or pernio-like acral lesions), other COVID-19 related skin lesions, necrotic skin lesions related to vasopressor use, or decubitus ulcers. We examine any affected areas, assess for healing, and evaluate for secondary infection. Wound care consultation may be warranted. Some patients recovering from COVID-19 have reported alopecia, which should be managed similarly to non-COVID-19 patients.

*Treatment for long-covid is largely symptomatic and based on therapies for treatment of similar conditions

References

https://pubmed-ncbi-nlm-nih-gov.myaccess.library.utoronto.ca/36215063/

https://www-uptodate-com.myaccess.library.utoronto.ca/contents/covid-19-evaluation-and-management-of-adults-with-persistent-symptoms-following-acute-illness-long-covid?search=long%20covid&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H3543077690

AL

Transfusion-associated circulatory overload (TACO)

TACO:

Transfusion-associated circulatory overload (TACO) is a complication of blood transfusions that occurs when the volume of transfused blood exceeds the capacity of the recipient's cardiovascular system.

Clinical Features: TACO can present with a range of clinical features, including dyspnea, orthopnea, cough, chest pain, tachycardia, and hypertension. These symptoms typically occur within six hours of the transfusion and may persist for several days. In severe cases, TACO can lead to acute respiratory distress syndrome (ARDS), which requires intensive care management.

Pathophysiology: The pathophysiology of TACO is complex and involves a combination of factors. The transfused blood increases the volume and viscosity of the recipient's blood, leading to increased pressure and strain on the cardiovascular system. This can result in increased pulmonary capillary pressure and decreased cardiac output, leading to pulmonary edema and respiratory distress. Other factors that may contribute to TACO include pre-existing cardiac or renal dysfunction, advanced age, and a history of blood transfusions.

Diagnosis: The diagnosis of TACO is based on clinical features, such as the onset of symptoms within six hours of the transfusion, along with evidence of fluid overload on chest X-ray or ultrasound. It is essential to differentiate TACO from other causes of respiratory distress, such as transfusion-related acute lung injury (TRALI), sepsis, and congestive heart failure (CHF). TRALI is a severe complication of blood transfusions that occurs due to an immune reaction to transfused antibodies, while sepsis and CHF may have similar clinical features to TACO.

Management: The management of TACO involves a combination of supportive measures and specific treatments. Supportive measures may include oxygen therapy, diuretics, and elevation of the head of the bed to reduce fluid overload. Specific treatments for TACO may include slowing the rate of transfusion, reducing the volume of transfused blood, or administering medications, such as vasodilators or inotropic agents, to improve cardiac function. In severe cases, mechanical ventilation may be necessary to manage respiratory distress and prevent the development of ARDS.

Prevention: Prevention of TACO involves careful selection of blood products and monitoring of recipients during and after transfusions. Blood products should be selected based on the recipient's blood type and any pre-existing medical conditions that may increase the risk of TACO. Monitoring during and after transfusions should include measurement of vital signs and assessment for signs of fluid overload or respiratory distress.

In conclusion, TACO is a common complication of blood transfusions that can lead to significant morbidity and mortality. Early recognition and management of TACO are essential to prevent the development of severe respiratory distress and ARDS. Careful selection of blood products and monitoring of recipients can help prevent the development of TACO and improve outcomes for transfusion recipients.

References:

1. Popovsky MA, Whitaker B, Arnold NL. Severe outcomes of transfusion (SHOT) initiative: analysis of the first two annual reports. Transfus Med Rev. 2005;19(4):284-295.
2. Gajic O, Rana R, Winters JL, et al. Transfusion-related acute lung injury in the critically ill: prospective nested case-control study. Am J Respir Crit Care Med. 2007;176(9):886-891.
3. Williamson LM, Lowe S, Love EM, Cohen H, Soldan K, McClelland DB. Serious hazards of transfusion.

- KM

Status Epilepticus

Status epilepticus is a medical emergency that occurs when a seizure lasts longer than five minutes or when seizures occur in rapid succession without the individual returning to their baseline level of consciousness in between. This condition requires immediate medical attention as it can be life-threatening and can cause permanent brain damage.

Epilepsy is a neurological disorder that affects about 1% of the population worldwide. Epileptic seizures are the hallmark of this condition and are caused by abnormal electrical activity in the brain. In most cases, seizures are brief and self-limited, lasting only a few seconds or minutes. However, in some cases, seizures can become prolonged and potentially life-threatening.
Status epilepticus can be classified into two main categories: convulsive and non-convulsive. Convulsive status epilepticus is characterized by tonic-clonic (grand mal) seizures, which involve muscle rigidity, jerking movements, and loss of consciousness. Non-convulsive status epilepticus is characterized by absence seizures or complex partial seizures, which may be more difficult to recognize as they do not involve convulsions or obvious motor manifestations.

The causes of status epilepticus are varied and can be related to the underlying condition that causes seizures. In some cases, status epilepticus may be triggered by an infection, a head injury, drug or alcohol abuse, or withdrawal from medication. It can also occur in people who have never had a seizure before, as a result of a stroke, brain tumor, or other neurological condition.

The diagnosis of status epilepticus is based on the clinical presentation and can be confirmed by electroencephalogram (EEG), which records the electrical activity of the brain. Magnetic resonance imaging (MRI) or computed tomography (CT) scans may also be performed to identify the underlying cause of the seizures.

Treatment of status epilepticus is aimed at stopping the seizures as quickly as possible to prevent brain damage and other complications. The first line of treatment is usually with benzodiazepines such as lorazepam, diazepam, or midazolam, which are administered intravenously. If seizures persist, additional medications such as phenytoin, fosphenytoin, or levetiracetam may be given. In some cases, anesthetic agents may be used to induce a coma-like state to control the seizures.
In addition to medical treatment, supportive care is also essential for people with status epilepticus. This may include respiratory support, hydration, and management of any other medical conditions that may be present. Close monitoring is also necessary to prevent complications such as aspiration pneumonia or the development of acute respiratory distress syndrome (ARDS).

The prognosis of status epilepticus depends on the underlying cause and the duration of the seizures. If treated promptly, most people with status epilepticus will recover without significant long-term complications. However, prolonged seizures can cause permanent brain damage, and in some cases, can be fatal.

In conclusion, status epilepticus is a medical emergency that requires immediate attention. It is essential to recognize the signs and symptoms of this condition and seek medical attention as soon as possible. Prompt treatment with appropriate medications and supportive care can help prevent complications and improve outcomes for people with status epilepticus.

References:
1. Convulsive status epilepticus in adults: Management - UptoDate
2.Status epilepticus - NEJM

- KM

Hypercalcemia

Hypercalcemia is defined as a total corrected serum calcium over 2.6mmol/L or ionized calcium over 1.35mmol/L. The first step in the evaluation of a patient with hypercalcemia is to verify with repeat measurement (total calcium corrected for albumin) that there is a true increase in the serum calcium concentration. The next step is to measure parathyroid hormone (PTH). PTH is a polypeptide secreted by the parathyroid gland in response to low calcium levels detected in the blood. PTH facilitates the synthesis of active vitamin D and calcitriol (1,25-dihydroxycholecalciferol) in the kidneys, and also regulates calcium and phosphate. PTH effects are present in the bones, kidneys, and small intestines. As serum calcium levels drop, the secretion of PTH by the parathyroid gland increases. If serum calcium is elevated, as in hypercalcemia, the parathyroid glands should stop the release of PTH. 

Therefore, in hypercalcemia, we would expect PTH to be lower than its normal range of 10 to 65 ng/L. If serum PTH is found to be elevated in the context of hypercalcemia, this indicates that the problem is PTH-dependent, and we should investigate the parathyroid gland for hyperparathyroidism. The next step is to get a 24-hour urinary calcium excretion. If this 24-hour level is high, you can diagnose your patient with a primary hyperparathyroidism. If this 24-hour urine calcium is low, you can diagnose your patient with familial hypocalciuric hypercalcemia (FHH). Its also important to check if your patient is taking lithium, as this can cause hyperparathyroidism as well. 

If PTH is normal or low in the context of hypercalcemia, this is considered a PTH-independent cause of hypercalcemia, and nonparathyroid causes of hypercalcemia such as thyrotoxicosis and malignancy must be considered. In the presence of low serum PTH concentrations (<20 pg/mL), vitamin D metabolites and Parathyroid hormone related protein (PTHrP) should be measured (25(OH)D, 1,25-dihydroxyvitamin D, PTHrP). An elevated serum concentration of 25(OH)D is indicative of vitamin D intoxication due to the ingestion of either vitamin D or calcidiol itself. Increased levels of 1,25-dihydroxyvitamin D may be induced by direct intake of this metabolite, extrarenal production in granulomatous diseases or lymphoma, or increased renal production that can be induced by primary hyperparathyroidism but not by PTHrP. If both of these are not elevated, but PTHrP is, we need to evaluated for malignancy. Specifically, we would be concerned for multiple myeloma (a hematological malignancy of plasma cells). Presentation of multiple myeloma includes hypercalcemia, renal failure, anemia, and bone pain. To evaluate for multiple myeloma, you should order a CBC (to look for normocytic anemia), serum protein electrophoresis (to look for monoclonal expansion), serum free light chains, bone marrow biopsy, and urinalysis. 

Other investigations that should be ordered for hypercalcemia include vitamin D, phosphorus, albumin, and urinalysis. If bone pain is a presenting symptom, an MRI of the area inducing pain may be warranted.

The treatment of hypercalcemia is as follows: 1) discontinue oral calcium supplements, 2) hydration with intravenous normal saline, 3) consider furosemide, and 4) give bisphosphonates (Pamidronate 60-90 mg IV or zoledronate 4mg IV). For refractory patients, you can consider calcitonin. 

References:

1. Diagnostic approach to hypercalcemia - UptoDate

2. Treatment of hypercalcemia - UptoDate

3. Physiology, Parathyroid Hormone - NCBI

-KM

Assessment of the Spleen

 

The Normal Spleen

The spleen lies within the peritoneal cavity in the posterior portion of the left upper quadrant. The normal size of the spleen correlates with a person's height, weight, and sex. In one study, the upper limits of normal for the tallest females and males were approximately 12.3 and 14.5 cm respectively. 

Common Terms Relating to the Spleen

Accessory spleen – A separate region of splenic tissue in the abdomen, present in approximately 15 percent of individuals.

Asplenia – Absence of the spleen or absent splenic function (also called functional asplenia or autosplenectomy). This may be caused by surgical splenectomy or a condition such as sickle cell disease in which splenic infarction early in life causes loss of splenic function. 

Hyposplenia – Reduced splenic function. Milder forms of sickle cell disease such as hemoglobin SC disease or sickle-beta+ thalassemia may cause hyposplenia. An autoimmune disorder in which T or B lymphocyte function is impaired may affect antibody production and/or cell-mediated immunity without impacting other functions. 

Splenomegaly – Increased spleen size. Non-pathologic anatomical variations are common, and mild deviations from the standard range may be normal.

Hypersplenism – Splenic sequestration and/or destruction of blood cells extensive enough to cause one or more cytopenias. 

Splenosis – Seeding of the abdominal cavity with splenic cells that can occur during surgery or trauma. 

Physical Exam Technique

Palpation

1. Start in RLQ
2. Get your fingers set then ask patient to take a deep breath. Don’t dip your fingers or push inwards.
3. When patient expires, take up new position.
4. Note lowest point of spleen below costal margin, texture of splenic contour, and tenderness
5. If spleen is not felt, repeat with pt lying on right side. Gravity may bring spleen within reach.

Note: Enlarged spleens can be fragile and easily injured on palpation, let the spleen touch your fingers and instead of aggressively digging for it!

Percussion

Castell's sign: place the patient in the supine position. With the patient in full inspiration and then full expiration, percuss the area of the lowest intercostal space in the left anterior axillary line. If the note changes from resonant on full expiration to dull on full inspiration, the sign is regarded as positive for splenomegaly.

Other

The use of bedside ultrasound may increase the sensitivity and specificity of the traditional physical examination in determining if the spleen is enlarged. 

References

https://www-uptodate-com.myaccess.library.utoronto.ca/contents/evaluation-of-splenomegaly-and-other-splenic-disorders-in-adults?search=splenomegaly&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1

https://stanfordmedicine25.stanford.edu/the25/spleen.html

https://pubmed-ncbi-nlm-nih-gov.myaccess.library.utoronto.ca/26509293/ 

A.L.

Approach to Hypothermia

Definition: Core body temperature <35 °C 

Normally, the body's autonomic system preserves the core temperature to 37 +/- 0.5 °C. In response to a cold stress, the hypothalamus attempts to stimulate heat production through shivering and increased thyroid, catecholamine, and adrenal activity. Sympathetically mediated vasoconstriction minimizes heat loss by reducing blood flow to peripheral tissues. In some cases, our body's regular mechanisms are overcome, or behavioural adaptations such as clothing and shelter are not available to protect against hypothermia.

Staging of Hypothermia
Mild hypothermia – Core temperature 32 to 35°C (90 to 95°F)
Moderate hypothermia – Core temperature 28 to 32°C (82 to 90°F)
Severe hypothermia – Core temperature <28°C (82°F)

Symptoms (presented in order of increasing severity)

• shivering,  tachypnea, tachycardia, initial hyperventilation, ataxia, dysarthria, impaired judgment, shivering, and "cold diuresis."
• reductions in pulse rate and cardiac output, hypoventilation, central nervous system depression, hyporeflexia, decreased renal blood flow, and loss of shivering at the lower end of the moderate hypothermia core temperature range. Paradoxical undressing may be observed. Atrial fibrillation, junctional bradycardia, and other arrhythmias can occur. The pupillary light reflex is depressed through slowing of both constriction and dilation. Dilated pupils are seen below a core temperature of approximately 29°C
• pulmonary edema, oliguria, areflexia, coma, hypotension, bradycardia, ventricular arrhythmias (including ventricular fibrillation), and asystole. Loss of corneal and oculocephalic reflexes may be noted.
• death

Differential Diagnosis

Broadly, hypothermia can be divided into environmental and non-environmental. Common environmental causes can include submersion in water and prolonged exposure to cold environments. 

Non-environmental causes of hypothermia include many illnesses.

• Decreased body heat generation (hypothyroid, adrenal insufficiency, hypoglycaemia, malnutrition)
• Impaired thermoregulation (CVA, CNS trauma, MS)
• Drugs/toxins (general anesthetics, ethanol, phenothiazines, barbiturates, antidepressants and organophosphate)
• Trauma (burns)
• Infection (sepsis)
• Other (vascular insufficiency, uraemia, iatrogenic, prolonged cardiac arrest)

Treatment

1. Resuscitation

Start with emergency management principles, including assessment of airway, breath and circulation. Endotracheal intubation is performed in patients with respiratory distress or those who cannot protect their airway. CPR may be required. Note peripheral pulses can be difficult to palpate in a vasoconstricted bradycardic patient. It is best to check for a central pulse for up to a full minute using a continuous-wave Doppler, if available. Alternatively, a focused bedside echocardiogram can be performed.

*Note: rough handling of the patient may precipitate arrhythmias, including ventricular fibrillation. Take care to avoid jostling the patient during the physical examination or the performance of essential procedures.

2. Rewarming 

Core temperature, ideally esophageal temperature in intubated patients, should be monitored closely to assess the adequacy of therapy and to prevent iatrogenic hyperthermia. Rewarming should begin as soon as possible. Rewarming techniques are divided into passive external rewarming, active external rewarming, and active internal core rewarming, and are used depending on severity of hypothermia. 

Passive external: after wet clothing is removed, the patient is covered with blankets or other types of insulation.

Active external:  warm blankets, heating pads, radiant heat, warm baths, or forced warm air is applied directly to the patient's skin.

Active internal: Endovascular temperature control catheters are preferred. If not available, irrigation of the peritoneum or the thorax (via the pleural space) with warmed isotonic crystalloid can be done.

3. Other

For patients who fail to rewarm appropriately despite aggressive rewarming measures, it is recommended to treat with empiric broad-spectrum antibiotics and a single dose of glucocorticoid (eg, dexamethasone 4 mg IV or hydrocortisone 100 mg IV). 

Concurrently, work-up should be completed to investigate underlying causes of hypothermia if unclear.

References

https://www-uptodate-com.myaccess.library.utoronto.ca/contents/accidental-hypothermia-in-adults?search=hypothermia%20treatment&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1

https://blackbook.ucalgary.ca/schemes/general/hypothermia/

A.L.