Communities Weekly Rewind: Confusing Case of Ovarian Hyperstimulation Syndrome

By Silvi Shah, MD, FASN, FACP

Introduction and BackgroundWeekly Rewind 1024x512 (004)_FINAL.png

An 18 year-old female presented with a 4 day history of non oliguric acute kidney injury (AKI), creatinine of 7.5 mg/dl, severe anemia (hemoglobin of 5.8 g/dl), and generalized edema following ovulation induction therapy. Corrected reticulocyte count was 0.15%.  Platelet and leukocyte counts were normal.  Other laboratory workup was as follows:

  • albumin 1.9 g/dl,
  • uric acid 6.5 mg/dl, and
  • LDH 330 U/L
  • C3 levels were low
  • C4 was normal
  • Antinuclear antibody serology, ANCA, and viral studies were negative
  • Urinalysis showed 3+ albumin, 50 RBCs, and 30 WBC’s
  • Spot urine pcr was 2.4 g/g


USG showed bilateral pleural effusion, bulky ovaries, normal kidneys size with increased echogenicity, but no ascites.  Her hospital course was further complicated by extensive colitis and foot drop.


Query and Hypothesis

The timing of this was highly suggestive of ovarian hyperstimulation syndrome, but many clinical factors did not fit this diagnosis.


Discussion

With clinical features of AKI and hemoconcentration, ovarian hyperstimulation syndrome (OHSS) was considered initially.  Even though the clinical picture masqueraded ovarian hyperstimulation syndrome, low C3 level, and active urinary sediment was concerning.  Furthermore, severe anemia (OHHS typically is severely hemoconcentrated) with lack of reticulocytosis, severe hypertension, and absence of ascites made capillary leak syndrome unlikely.  Due to confusing picture, a renal biopsy was suggested to rule out glomerulonephritis and thrombotic microangiopathy (TMA).  Surprisingly, a renal biopsy showed pauci immune crescentic glomerulonephritis and she was started on treatment for vasculitis.


What is the pathophysiology of AKI in ovarian hyperstimulation syndrome?

The OHHS is characterized by cystic enlargement of the ovaries, and ovarian neoangiogenesis.  The early form of OHSS, is related to an exaggerated ovarian response to gonadotrophin stimulation, whereas the late form (10 days after hCG), mainly occurs due to the secretion of placental hCG.  The pathophysiology of OHSS is unknown, but the process is related to increased vascular permeability due to increased secretion of vasoactive substances such as interleukins, tumor necrosis factor (TNF)-α, endothelin-1, and VEGF by the ovaries.  Due to increased capillary permeability, there is a fluid shift from the intravascular to the third space leading to intravascular depletion, and AKI.  The hypovolemia of OHSS further lead to hemoconcentration and a hypercoagulable state.  Additionally, AKI may occur due to microthrombi in the tubules and decreased renal perfusion.  Excess VEGF has also been implicated in collapsing FSGS in HIVAN, multicentric Castleman's disease, and POEMS syndrome.

What are the other clinical manifestations of ovarian hyperstimulation syndrome?

Enlargement of ovaries results in abdominal pain, nausea, and vomiting.  Ascites is commonly seen due to increased capillary permeability.  Hemoconcentration and hypovolemia occurs due to third space fluid shift, which further predisposes to AKI.  Decreased renal perfusion results in increased reabsorption of sodium and water in the proximal tubule, and decreased exchange of hydrogen and potassium for sodium in the distal tubule resulting in hyperkalemia and acidosis.  Patients have an increased risk of developing deep venous thrombosisand pulmonary embolism.  In rare cases, complications of ovarian torsion and peritonitis can occur.

What is the treatment of ovarian hyperstimulation syndrome?

Since OHSS is a self-limiting disease, treatment should be conservative and directed at symptoms.  Women with mild disease should be closely monitored for enlarging abdominal girth, and acute weight gain.  Medical treatment of severe hyperstimulation is fluid management and correction of hypovolemia.  To prevent thrombosis, subcutaneous heparin is started prophylactically on hospital admission.  Paracentesis is indicated for ascites if the patient has severe abdominal discomfort, pulmonary or renal compromise.  Surgery may be necessary in extreme cases, such as a ruptured cyst, ovarian torsion, or internal hemorrhage.

Please read the full discussion at ASN Communities.

Category:
Subcategory:
Author:
Silvi Shah, MD, FASN, FACP
Body:

Introduction and BackgroundWeekly Rewind 1024x512 (004)_FINAL.png

An 18 year-old female presented with a 4 day history of non oliguric acute kidney injury (AKI), creatinine of 7.5 mg/dl, severe anemia (hemoglobin of 5.8 g/dl), and generalized edema following ovulation induction therapy. Corrected reticulocyte count was 0.15%.  Platelet and leukocyte counts were normal.  Other laboratory workup was as follows:

  • albumin 1.9 g/dl,
  • uric acid 6.5 mg/dl, and
  • LDH 330 U/L
  • C3 levels were low
  • C4 was normal
  • Antinuclear antibody serology, ANCA, and viral studies were negative
  • Urinalysis showed 3+ albumin, 50 RBCs, and 30 WBC’s
  • Spot urine pcr was 2.4 g/g


USG showed bilateral pleural effusion, bulky ovaries, normal kidneys size with increased echogenicity, but no ascites.  Her hospital course was further complicated by extensive colitis and foot drop.


Query and Hypothesis

The timing of this was highly suggestive of ovarian hyperstimulation syndrome, but many clinical factors did not fit this diagnosis.


Discussion

With clinical features of AKI and hemoconcentration, ovarian hyperstimulation syndrome (OHSS) was considered initially.  Even though the clinical picture masqueraded ovarian hyperstimulation syndrome, low C3 level, and active urinary sediment was concerning.  Furthermore, severe anemia (OHHS typically is severely hemoconcentrated) with lack of reticulocytosis, severe hypertension, and absence of ascites made capillary leak syndrome unlikely.  Due to confusing picture, a renal biopsy was suggested to rule out glomerulonephritis and thrombotic microangiopathy (TMA).  Surprisingly, a renal biopsy showed pauci immune crescentic glomerulonephritis and she was started on treatment for vasculitis.


What is the pathophysiology of AKI in ovarian hyperstimulation syndrome?

The OHHS is characterized by cystic enlargement of the ovaries, and ovarian neoangiogenesis.  The early form of OHSS, is related to an exaggerated ovarian response to gonadotrophin stimulation, whereas the late form (10 days after hCG), mainly occurs due to the secretion of placental hCG.  The pathophysiology of OHSS is unknown, but the process is related to increased vascular permeability due to increased secretion of vasoactive substances such as interleukins, tumor necrosis factor (TNF)-α, endothelin-1, and VEGF by the ovaries.  Due to increased capillary permeability, there is a fluid shift from the intravascular to the third space leading to intravascular depletion, and AKI.  The hypovolemia of OHSS further lead to hemoconcentration and a hypercoagulable state.  Additionally, AKI may occur due to microthrombi in the tubules and decreased renal perfusion.  Excess VEGF has also been implicated in collapsing FSGS in HIVAN, multicentric Castleman's disease, and POEMS syndrome.

What are the other clinical manifestations of ovarian hyperstimulation syndrome?

Enlargement of ovaries results in abdominal pain, nausea, and vomiting.  Ascites is commonly seen due to increased capillary permeability.  Hemoconcentration and hypovolemia occurs due to third space fluid shift, which further predisposes to AKI.  Decreased renal perfusion results in increased reabsorption of sodium and water in the proximal tubule, and decreased exchange of hydrogen and potassium for sodium in the distal tubule resulting in hyperkalemia and acidosis.  Patients have an increased risk of developing deep venous thrombosisand pulmonary embolism.  In rare cases, complications of ovarian torsion and peritonitis can occur.

What is the treatment of ovarian hyperstimulation syndrome?

Since OHSS is a self-limiting disease, treatment should be conservative and directed at symptoms.  Women with mild disease should be closely monitored for enlarging abdominal girth, and acute weight gain.  Medical treatment of severe hyperstimulation is fluid management and correction of hypovolemia.  To prevent thrombosis, subcutaneous heparin is started prophylactically on hospital admission.  Paracentesis is indicated for ascites if the patient has severe abdominal discomfort, pulmonary or renal compromise.  Surgery may be necessary in extreme cases, such as a ruptured cyst, ovarian torsion, or internal hemorrhage.

Please read the full discussion at ASN Communities.

Area(s) of Interest:
Date:
Thursday, March 15, 2018