Nutcracker phenomenon

Nutcracker phenomenon, also known as left renal vein entrapment, refers to compression of the left renal vein, most commonly between the aorta and the superior mesenteric artery, with impaired blood outflow often accompanied by distention of the distal portion of the vein. Normally, the left renal vein brings blood out of the left kidney and into the inferior vena cava, the body’s largest vein. Compression of the left renal vein can cause blood to flow backward into other nearby veins.

The term nutcracker syndrome most often refers to the classic symptoms that can arise from the nutcracker phenomenon, e.g. hematuria, abdominal pain (classically left flank or pelvic pain) and orthostatic proteinuria. Some patients with nutcracker phenomenon don't have all of these classic symptoms though (hematuria, for example, is obligatory in nutcracker syndrome ), but still suffers from other symptoms arising from this vein compression disorder. Hence, both the terms nutcracker syndrome and nutcracker phenomenon can be used to describe symptomatic left renal vein entrapment. There's a wide spectrum of clinical presentations and diagnostic criteria are not well defined, which frequently results in delayed or incorrect diagnosis.

Nutcracker phenomenon has been linked to CFS and dysautonomia in several medical journal articles, both in pediatric and adult patients. Theories regarding the various ways in which nutcracker phenomenon can cause these symptoms include:
 * 1) severe congestion in the kidney may cause the expansion of the renal venous bed, which would affect the renin-angiotensin system.
 * 2) severe congestion in the adrenal medulla, which is innervated by sympathetic nerves, may disturb a complex set of central neural connections controlling the sympathoadrenal system.
 * 3) overproduction or night retention of catecholamines.

Signs and symptoms
The symptoms and severity of renal nutcracker phenomenon can vary from person to person. Some people may not have any symptoms (especially children), while others have severe and persistent symptoms. Symptoms are often worsened by physical activity.

Signs and symptoms may include:
 * Blood in the urine (hematuria) which can occasionally cause anemia requiring blood transfusions.
 * Abdominal or flank pain that may radiate to the thigh and buttock. Pain may be worsened by sitting, standing, walking, or riding in a vehicle that shakes.
 * Varicocele in men - almost always occurring on the left side.
 * Chronic fatigue syndrome and fatigue symptoms.
 * Pelvic congestion syndrome, causing symptoms such as chronic pelvic pain, pain during intercourse, painful or difficult urination, painful menstrual cramps during periods, and polycystic ovaries.
 * Orthostatic proteinuria.
 * Orthostatic intolerance (feeling light-headed or having palpitations when standing upright).
 * Tachycardia
 * Headache
 * Syncope
 * Nausea

Paper # 1
Hammami et al. published a case-study on a 24-year-old male who had a seven-year history of chronic fatigue syndrome, chronic pelvic pain syndrome, and vague abdominal pain. He also suffered from orthostatic hypotension, and he showed a possible tachycardic response during a tilt table test. He also reported symptoms of “slowed thinking” and an inability to exercise without feeling lightheaded. He underwent surgery to insert a left renal vein stent. His symptoms resolved soon after the intervention.

Paper # 2
This paper was titled "Does severe nutcracker phenomenon cause pediatric chronic fatigue?". According to Takahashi, Ohta et al. (2000) 9 pediatric CFS patients at their clinic were intermittently or persistently absent from school. The patients had been suspected to be burdened with psychosomatic disorders, having orthostatic hypotension, postural tachycardia, or other autonomic dysfunction symptoms. When they investigated the cause of moderate orthostatic proteinuria in some of the patients, they found by chance that they suffered from severe nutcracker phenomenon (NC). Further investigation revealed that nutcracker phenomenon was present in all 9 children complaining of chronic fatigue, even those who did not have orthostatic proteinuria. They conclude in their abstract: "Their symptoms filled the criteria of chronic fatigue syndrome or idiopathic chronic fatigue (CFS/CF). An association between severe NC and autonomic dysfunction symptoms in children with CFS/CF has been presented."

Shin (2006) and the Dysautonomia Information Network describe the findings further. The patients are reported to have suffered from a broad range of symptoms including; chronic fatigue, headache, lightheadedness, dizziness, abdominal pain, unrefreshing sleep, muscle pain, joint pain, sore throat, low-grade fever, afebrile chills in hot summer and depression.

The authors of this study point out that the classic symptom of nutcracker phenomnen is renal bleeding (presenting as micro or macro-hematuria). In their experience, non-CFS patients with nutcracker phenomenon typically had hematuria, but the patients with CFS-associated nutcracker phenimenon had no renal bleeding. Some of these patients did report fibromyalgia type pain. Some patients had proteinuria, others had no urinary abnormalities. The authors of this study had some theories regarding the various ways in which nutcracker phenomenon might affect autonomic function: First, severe congestion in the kidney may cause the expansion of the renal venous bed, which would affect the renin-angiotensin system. Secondly, severe congestion in the adrenal medulla, which is innervated by sympathetic nerves, may disturb a complex set of central neural connections controlling the sympathoadrenal system. On the other hand, overproduction or night retention of catecholamines might be responsible for the various symptoms of pediatric chronic fatigue syndrome.

Paper # 3
Another paper from Takahashi et al. was titled "An effective "transluminal balloon angioplasty" therapy for pediatric chronic fatigue syndrome with nutcracker phenomenon". Unfortunately, the abstract and full-text are not easily found, but another paper describes the findings in this paper.

It's about a 13 year old girl who suffered from orthostatic hypotension, tachycardia and chronic fatigue syndrome. The patient was also diagnosed with nutcracker phenomenon, and was successfully treated with transluminal balloon angioplasty of the compressed left renal vein between the aorta and superior mesenteric artery. Both her dysautonomia and CFS improved after the intervention.

Paper # 4
A third paper from Takahashi et al. was titled "An ultrasonographic classification for diverse clinical symptoms of pediatric nutcracker phenomenon". They tested 93 pediatric patients for nutcracker phenomenon (56 with idiopathic renal bleeding, 14 with massive orthostatic proteinuria and 23 with severe orthostatic intolerance). Left renal vein occlusion (nutcracker phenomenon) was observed in 70% of the patients with severe orthostatic intolerance, and in contrast in 18% and 14% for idiopathic renal bleeding and massive orthostatic proteinuria, respectively.

Paper # 5
Takemura et al. published a paper describing four adolescents diagnosed with nutcracker syndrome. Three of these patients had previously been diagnosed with orthostatic disturbance and suffered from various symptoms including fainting, tachycardia, headache and abdominal pain.

Paper # 6
A case-report from Daily et al. titled "Nutcracker syndrome: symptoms of syncope and hypotension improved following endovascular stenting" describes a 19-year-old woman diagnosed with nutcracker syndrome. She suffered from syncope, sometimes multiple episodes in one day. Her other symptoms included unilateral hematuria, nausea, lower abdominal pain and weight loss. After she was treated with stenting of her left renal vein, her symptoms improved drastically and she had no episodes of syncope and her blood pressure normalized.

Paper # 7
In a paper titled "Newly-identified symptoms of left renal vein entrapment syndrome mimicking orthostatic disturbance," Koshimichi et al. describes the symptoms of 53 pediatric patients diagnosed with left renal vein entrapment syndrom (another term for nutcracker phenomenon). 22 of these 53 patients (42%) suffered from orthostatic disturbance. 15 of these 22 patients suffered from general malaise and fatigue, palpitation or shortness of breath in 14, severe abdominal pain in 10, increased pulse (21 beats per minute or more) on standing in 2 patients.

There was an absence of micro/macro-hematuria 11 of these 22 patients. 13 of 22 patients had no proteinuria. 4 of 22 patients had neither micro/macro-hematuria or proteinuria.

Treatment with midodrine significantly decreased orthostasis scores. The most severe patients (6 of 22) had either low urinary cortisol or plasma cortisol, persistent in some and intermittent in some. These patients improved after being given a low oral dose of fludrocortisone acetate to maintain sufficient blood cortisol.

Epidemiology
Nutcracker syndrome/phenomenon is often described as "rare" in the medical literature, even though there's research indicating that it's a severely under-diagnosed condition.

Varicocele is a known complication of nutcracker phenomenon. Between 9.5% and 15% of all men globally are affected by varicocele. According to two separate studies, 30% to 100% of varicocele patients have nutcracker phenomenon. If one extrapolates these numbers, between 2.9-15% of all men suffer from nutcracker phenomenon. A minuscule percentage of these patients are ever diagnosed with nutcracker phenomenon.

There might be several reasons behind this under-diagnosing, including:
 * 1) wide spectrum of symptoms,        many of which are not well known in the medical community to be linked to nutcracker phenomenon.
 * 2) not all patients experience classic nutcracker syndrome symptoms like hematuria, abdominal pain, proteinuria
 * 3) diagnostic criteria are not well defined
 * 4) nutcracker phenomenon is not easily detectable using conventional means. Standard CT is for example insufficient to diagnose nutcracker phenomenon.

Diagnosis
This quote is from Dysautonomia Information Network's website, where Dr. Takahashi (the author of some of the studies linking nutcracker phenomenon to CFS & orthostatic intolerance) explains the methods used to diagnose nutcracker phenomenon:

"The methods used to diagnose nutcracker phenomenon include Doppler US, MRI and three-dimensional helical computed tomography. Dr. Takahashi (personal communication, September 8, 2002) explains the procedures for testing as follows: Conventional ultrasound requires patients to be examined for left renal vein obstruction in 4 positions: supine, semisitting, upright and prone. Nonvisualization of the left renal vein lumen or absence of the left renal vein wall between the aorta and superior mesenteric artery is regarded as signifying left renal vein obstruction. Doppler color flow imaging can be used to locate a blue-colored blood stream flowing to the dorsal direction. This is a collateral vein flowing from the left renal vein into the paravertebral vein. With MRI, oblique coronal images along the left renal vein, and also axial images, are recommended to visualize the collateral veins around the left renal vein."

Notable studies

 * 2000, An effective "transluminal balloon angioplasty" therapy for pediatric chronic fatigue syndrome with nutcracker phenomenon - (Abstract)
 * 2000, Clinical and radiological features in four adolescents with nutcracker syndrome - (Abstract)
 * 2017, A Tough Nut to Crack: Chronic Fatigue Syndrome and Abdominal Pain Attributed to Nutcracker Syndrome - (Full text)

Learn more

 * Renal nutcracker syndrome - Genetic and Rare Diseases Information Center
 * Nutcracker Syndrome - Wikipedia
 * Renal Vein Entrapment And Orthostatic Intolerance - DINET