Abdominal pain is present in nearly half of patients with DKA and its intensity is associated with worsening metabolic acidosis.⁹ The mechanism of abdominal pain in DKA is poorly understood, however gastritis, gastric distension and ileus secondary to metabolic derangement have been suggested.¹⁰ While abdominal pain in DKA is most often non-specific in up to 30% of cases pain is actually secondary to the stressor that precipitated the DKA state.^9–11 Fluid resuscitation and insulin are the mainstays of therapy of DKA, however abdominal pain that persists despite correction of acidosis warrants further investigation.^11,12 While abdominal manifestations are common in DKA they are not commonly seen in hyperosmolar hyperglycemic syndromes.¹²

Alcoholic ketoacidosis also commonly presents with abdominal pain and similarly to DKA gastrointestinal symptoms may be multifactorial in etiology. There is a direct gastritis effect by alcohol and a secondary effect induced by ketoacidosis on gastric functioning leading to nausea, vomiting, and abdominal pain.¹³

Adrenal insufficiency occurs when adrenal gland function is reduced by lack of adrenocorticotropic hormone (ACTH), chronic steroid use, or primary adrenal disease and, as a result, glucocorticoid production is unable to meet physiologic demands. Adrenal (addisonian) crisis generally occurs in patients with underlying adrenal insufficiency in the setting of a physiologic stressor or medical noncompliance; however, it may also occur in normal patients in the settings of blunt trauma, sepsis, meningococcemia, emboli, and other critical illnesses.¹⁴ Symptoms can be acute or insidious at onset but may include weakness, fatigue, prostration, confusion, vomiting, diarrhea, fever, hypotension, tachycardia, shock, and abdominal pain.¹⁴ Any of these symptoms in a patient who has been taking steroids for more than a week should prompt consideration of addisonian crisis. The abdominal pain may be severe, causing suspicion of an intra-abdominal catastrophe.^15,16 The basis of the abdominal pain is unknown, although there is evidence to suggest that gastric dysmotility and serositis occur.^17,18 Hypoglycemia (with concomitant mineralocorticoid deficiency), hyponatremia, and hyperkalemia may occur in acute crisis but are more common in chronic deficiency. Recommended treatment is intravenous dexamethasone. Hydrocortisone may also be used but has the drawback of interfering with ACTH stimulation testing.¹⁹

Although abdominal complaints receive scant attention in most texts, they are fairly common in thyrotoxicosis and include nausea, vomiting, loose frequent stools, and weight loss. Perhaps they are overlooked because of the protean and more life-threatening derangements of this disease.²⁰ In 1 retrospective series, GI symptoms occurred in 36% of cases.²¹ Although most patients with abdominal pain and thyrotoxicosis have no demonstrable intra-abdominal pathologic condition, in 1 case series, 16% had an intra-abdominal cause requiring surgery, serving as a reminder that the search for serious medical conditions that have precipitated thyroid storm should not be overlooked.²²

Acute intermittent porphyria is a rare autosomal dominant condition that presents most commonly with abdominal pain.²³ With variations in penetrance and expressivity, the gene is symptomatic in 1 to 2 persons per 100,000.²⁴ The mutation leads to a deficiency of porphobilinogen deaminase, a hepatic enzyme involved in heme synthesis. δ-Aminolevulinic acid and porphobilinogen accumulate in tissues, leading to a neurovisceral crisis that results in acute abdominal pain. Attacks can be precipitated by stimulation of the cytochrome P450 system with medications (eg, rifampin, barbiturates, and sulfonamides), estrogens or progesterones, smoking, or alcohol. Attacks may also occur when heme oxygenase is induced by physiologic stressors such as fever, fasting, or infection.^23,24 Pain is thought to be caused by visceral autonomic neuropathy leading to regions of overactive and underactive bowel. Pain may be persistent or colicky and is usually located in the lower part of the abdomen but may also occur in the back or lower limbs.²⁵ Other symptoms include fever, vomiting, constipation, weakness, muscle cramps, paresthesias, seizures, and neuropsychiatric complaints, including anxiety and depression. Dysautonomias can cause extra-abdominal symptoms with diaphoresis, flushing, tachycardia, and hypertension or hypotension. Seizures are generally because of hyponatremia, which may be secondary to vomiting or to the syndrome of inappropriate antidiuretic hormone hypersecretion. Neuropathy may be rapid and severe, leading to life-threatening respiratory involvement. The abdomen is usually soft, with only mild tenderness. Diagnosis is made by detecting elevated urinary porphobilinogen levels. Short-term management involves pain control, resuscitation, and evaluation for potentially life-threatening complications such as respiratory compromise from phrenic neuropathy or hyponatremia.²⁶

C1 inhibitor (C1INH) deficiency may be hereditary or acquired and results in angioedema involving the skin, GI tract, or upper airway. Excess active C1 leads to excessive complement activation and overproduction of bradykinin, resulting in submucosal and subcutaneous vascular permeability.²⁷ Approximately 25% of patients with C1INH deficiency have predominantly abdominal symptoms.²⁸ Submucosal edema in the stomach and small bowel leads to episodes of nausea, vomiting, and cramping abdominal pain. Abdominal examination may reveal marked tenderness, guarding, or rigidity, leading to the consideration of intra-abdominal surgical emergencies. Acute attacks may occur without any apparent cause but are more often precipitated by minor trauma (especially dental procedures), menstruation, stress, or use of angiotensin-converting enzyme inhibitors. The diagnosis may be suggested by a history of chronic abdominal complaints with episodic exacerbation. Abdominal symptoms generally precede cutaneous or upper airway symptoms.^29,30 Laryngeal edema, when present, is life threatening. Until recently, management involved airway control and standard supportive care.³¹ In October 2009, C1 esterase inhibitor replacement protein was approved by the Food and Drug Administration. Early trials have shown significant improvement of symptoms in acute attacks.³²

Hypercalcemia is most commonly caused by hyperparathyroidism and malignancy.³³ Elevated calcium levels affect nerve conduction, cardiac rhythm, function of cardiac and skeletal muscles, renal function, and GI motility. Patients may present with isolated abdominal pain that may be multifactorial in etiology.³⁴ Ileus formation leads to abdominal pain, nausea, and vomiting. Elevated levels of gastrin and lower stomach pH predispose patients to gastritis and peptic ulcer formation. Increased secretion of pancreatic enzymes may lead to acute pancreatitis. In the kidneys, in addition to tubular dysfunction that results in fluid and electrolyte losses, calcium deposition may lead to kidney stone formation and ureterolithiasis.³³ The diagnosis should be considered in patients with diffuse abdominal pain accompanied by weakness, lethargy, and dehydration.

Sickle cell disease is an autosomal recessive hemoglobinopathy characterized by production of hemoglobin S, which causes erythrocyte sickling, leading to chronic hemolytic anemia and recurrent vascular occlusion. Vascular occlusion can cause ischemia or infarction in almost any organ. In the abdomen, this may cause pain by a variety of mechanisms including local ischemia, microinfarction, macroinfarction (eg, of the spleen), cholelithiasis, cholecystitis, pancreatitis, splenic sequestration, hepatic crisis, and intrahepatic cholestasis.³⁵ Even in the absence of a surgical cause, ischemia and microinfarction can result in an examination that strongly suggests an acute surgical abdomen with peritoneal signs and leukocytosis. The clinician is guided by the patient’s description of previous episodes of painful crisis, but in uncertain cases, the increasing availability of bedside ultrasonography and abdominal computed tomography (CT) have made appropriate diagnosis of these patients’ condition easier. Crises can be triggered by many factors including infection, dehydration, cold, stress, menses, alcohol consumption, and hypoxemia; however, most of the time, there is no identifiable cause.

Abdominal pain in patients with neutropenia may be caused by a spectrum of disorders of the ileocecal region that ranges in severity from mild mucosal inflammation to bacterial and fungal invasion of the bowel, leading to transmural ulceration and/or necrotizing colitis with high mortality rates. The disorder has been variously named neutropenic enterocolitis (NE), typhlitis, and ileocecal syndrome. It is usually seen in patients receiving chemotherapy but occasionally occurs in patients with aplastic anemia, cyclic neutropenia, and AIDS.³⁶ Presentation is most likely 10 to 14 days after chemotherapy, coincident with the neutrophil nadir. The ileum, cecum, ascending colon, and appendix are the most common sites; however, any portion of the bowel may be affected. Abdominal symptoms in these patients may be masked due to immunosuppression, which inhibits elaboration of the inflammatory mediators that are the primary stimulators of intra-abdominal nociceptors; although focal right lower quadrant pain, abdominal distension, diarrhea, or rebound tenderness may be present.³⁷ Neutropenia with fever, abdominal pain, and diarrhea should prompt suspicion. Clostridium difficile enterocolitis, appendicitis, and diverticulitis are also diagnostic considerations in these patients. CT scan is the preferred diagnostic modality and reveals bowel wall thickening often involving the terminal ileum.³⁸ C difficile colitis is not usually limited to the cecum and rarely involves the ileum in contrast to NE. Ultrasonography has been shown to be useful in the diagnosis and management of critically ill patients in whom CT cannot be obtained. Ultrasonography reveals the affected bowel as a mass with a hyperechoic core and thick hypoechoic walls. In the setting of the abovementioned symptoms, a bowel wall thickness of 4 mm is considered diagnostic and increasing thickness correlates with disease severity.³⁹ Historically, surgery (right hemicolectomy) was the mainstay of treatment. More recent case series support medical management, including therapy with broad spectrum and antifungal antibiotics, and supportive care. Surgery may still be necessary in some patients, and early consultation is often warranted.⁴⁰